11-792692-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001191061.2(SLC25A22):c.448C>G(p.Leu150Val) variant causes a missense change. The variant allele was found at a frequency of 0.0744 in 1,553,550 control chromosomes in the GnomAD database, including 4,773 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 322 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4451 hom. )

Consequence

SLC25A22
NM_001191061.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.86

Publications

14 publications found

Variant links:

Genes affected

SLC25A22 (HGNC:19954): (solute carrier family 25 member 22) This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jul 2010]

SLC25A22 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
developmental and epileptic encephalopathy, 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
early myoclonic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC25A22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020220578).

BP6

Variant 11-792692-G-C is Benign according to our data. Variant chr11-792692-G-C is described in ClinVar as Benign. ClinVar VariationId is 139137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2 link	c.448C>G	p.Leu150Val	missense_variant	Exon 7 of 10	ENST00000628067.3	NP_001177990.1	Q9H936

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3 link	c.448C>G	p.Leu150Val	missense_variant	Exon 7 of 10	1	NM_001191061.2	ENSP00000486058.1		Q9H936

Frequencies

GnomAD3 genomes

AF:

0.0601

AC:

9153

AN:

152174

Hom.:

322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.0540

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0846

Gnomad OTH

AF:

0.0680

GnomAD2 exomes

AF:

0.0526

AC:

8328

AN:

158250

AF XY:

0.0520

show subpopulations

Gnomad AFR exome

AF:

0.0428

Gnomad AMR exome

AF:

0.0290

Gnomad ASJ exome

AF:

0.0606

Gnomad EAS exome

AF:

0.000248

Gnomad FIN exome

AF:

0.0572

Gnomad NFE exome

AF:

0.0831

Gnomad OTH exome

AF:

0.0638

GnomAD4 exome

AF:

0.0759

AC:

106389

AN:

1401258

Hom.:

4451

Cov.:

AF XY:

0.0748

AC XY:

51858

AN XY:

693128

show subpopulations

African (AFR)

AF:

0.0401

AC:

1294

AN:

32240

American (AMR)

AF:

0.0315

AC:

1158

AN:

36808

Ashkenazi Jewish (ASJ)

AF:

0.0627

AC:

1586

AN:

25298

East Asian (EAS)

AF:

0.000109

AC:

AN:

36768

South Asian (SAS)

AF:

0.0212

AC:

1723

AN:

81278

European-Finnish (FIN)

AF:

0.0581

AC:

2321

AN:

39932

Middle Eastern (MID)

AF:

0.0391

AC:

223

AN:

5706

European-Non Finnish (NFE)

AF:

0.0867

AC:

94072

AN:

1084876

Other (OTH)

AF:

0.0687

AC:

4008

AN:

58352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6641

13282

19924

26565

33206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3462

6924

10386

13848

17310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0601

AC:

9148

AN:

152292

Hom.:

322

Cov.:

AF XY:

0.0572

AC XY:

4260

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0406

AC:

1688

AN:

41558

American (AMR)

AF:

0.0397

AC:

608

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0168

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0540

AC:

574

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0845

AC:

5749

AN:

68000

Other (OTH)

AF:

0.0668

AC:

141

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

457

914

1370

1827

2284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0730

Hom.:

102

Bravo

AF:

0.0586

TwinsUK

AF:

0.0866

AC:

321

ALSPAC

AF:

0.0872

AC:

336

ESP6500AA

AF:

0.0345

AC:

147

ESP6500EA

AF:

0.0726

AC:

607

ExAC

AF:

0.0372

AC:

4254

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 12, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 04, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Developmental and epileptic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Early myoclonic encephalopathy

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.038

T;T;T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.64

.;.;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

L;L;L;.;.;.;.;.;.;.;.

PhyloP100

3.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.49

N;.;N;N;.;N;.;.;.;.;.

REVEL

Benign

0.22

Sift

Benign

0.51

T;.;T;T;.;T;.;.;.;.;.

Sift4G

Benign

0.36

T;T;T;T;T;.;T;T;T;.;T

Polyphen

0.0020

B;B;B;.;.;.;.;.;.;.;.

Vest4

0.17

MPC

0.45

ClinPred

0.0043

GERP RS

3.4

Varity_R

0.077

gMVP

0.70

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over