chr11-791990-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_001191061.2(SLC25A22):c.897C>T(p.Phe299Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000485 in 1,609,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SLC25A22
NM_001191061.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -0.626

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-791990-G-A is Benign according to our data. Variant chr11-791990-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 159918.

BP7

Synonymous conserved (PhyloP=-0.626 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000131 (20/152368) while in subpopulation AMR AF = 0.000588 (9/15312). AF 95% confidence interval is 0.000306. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2 link	c.897C>T	p.Phe299Phe	synonymous_variant	Exon 10 of 10	ENST00000628067.3	NP_001177990.1	Q9H936

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A22	ENST00000628067.3 link	c.897C>T	p.Phe299Phe	synonymous_variant	Exon 10 of 10	1	NM_001191061.2	ENSP00000486058.1	Q9H936
SLC25A22	ENST00000320230.9 link	c.897C>T	p.Phe299Phe	synonymous_variant	Exon 10 of 10	1		ENSP00000322020.5	Q9H936
SLC25A22	ENST00000531214.5 link	c.897C>T	p.Phe299Phe	synonymous_variant	Exon 10 of 10	2		ENSP00000437236.1	Q9H936
SLC25A22	ENST00000481290.5 link	c.*33C>T		downstream_gene_variant		5		ENSP00000431829.2	E9PJH7

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.0000633

AC:

AN:

236914

AF XY:

0.0000770

show subpopulations

Gnomad AFR exome

AF:

0.0000680

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000572

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000398

AC:

AN:

1456754

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

724660

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33364

American (AMR)

AF:

0.0000900

AC:

AN:

44462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39578

South Asian (SAS)

AF:

0.0000466

AC:

AN:

85892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4910

European-Non Finnish (NFE)

AF:

0.0000414

AC:

AN:

1110944

Other (OTH)

AF:

0.0000166

AC:

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000131

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41594

American (AMR)

AF:

0.000588

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000543

Hom.:

Bravo

AF:

0.000128

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Early myoclonic encephalopathy

Uncertain:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy

Benign:1

Oct 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SLC25A22-related disorder

Benign:1

Aug 13, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.5

(source)

DANN

Benign

0.83

PhyloP100

-0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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