rs111277421

Variant names:

Your query was ambiguous. Multiple possible variants found:

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), PanelApp Australia, 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191061.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A22	NM_001191061.2	MANE Select	c.448C>G	p.Leu150Val	missense	Exon 7 of 10	NP_001177990.1	Q9H936
SLC25A22	NM_001425334.1		c.523C>G	p.Leu175Val	missense	Exon 7 of 10	NP_001412263.1
SLC25A22	NM_001425335.1		c.487C>G	p.Leu163Val	missense	Exon 7 of 10	NP_001412264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.448C>G	p.Leu150Val	missense	Exon 7 of 10	ENSP00000486058.1	Q9H936
SLC25A22	ENST00000320230.9	TSL:1	c.448C>G	p.Leu150Val	missense	Exon 7 of 10	ENSP00000322020.5	Q9H936
SLC25A22	ENST00000860087.1		c.523C>G	p.Leu175Val	missense	Exon 7 of 10	ENSP00000530146.1

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Developmental and epileptic encephalopathy (1)

Early myoclonic encephalopathy (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

PhyloP100

3.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.49

REVEL

Benign

0.22

Sift

Benign

0.51

Sift4G

Benign

0.36

Polyphen

0.0020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over