Variant rs80335370 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001191061.2(SLC25A22):c.234C>T(p.Pro78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,611,342 control chromosomes in the GnomAD database, including 12,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 762 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11608 hom. )

Consequence

SLC25A22
NM_001191061.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.35

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-793588-G-A is Benign according to our data. Variant chr11-793588-G-A is described in ClinVar as [Benign]. Clinvar id is 159913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A22	NM_001191061.2 linkuse as main transcript	c.234C>T	p.Pro78=	synonymous_variant	5/10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3 linkuse as main transcript	c.234C>T	p.Pro78=	synonymous_variant	5/10	1	NM_001191061.2	ENSP00000486058	P1

Frequencies

GnomAD3 genomes

AF:

0.0941

AC:

14308

AN:

152044

Hom.:

763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.0915

Gnomad ASJ

AF:

0.0568

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.0825

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.0784

GnomAD3 exomes

AF:

0.0965

AC:

24059

AN:

249224

Hom.:

1350

AF XY:

0.0984

AC XY:

13286

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.0420

Gnomad AMR exome

AF:

0.0675

Gnomad ASJ exome

AF:

0.0626

Gnomad EAS exome

AF:

0.0641

Gnomad SAS exome

AF:

0.0751

Gnomad FIN exome

AF:

0.0992

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.0988

GnomAD4 exome

AF:

0.122

AC:

178487

AN:

1459180

Hom.:

11608

Cov.:

AF XY:

0.121

AC XY:

87839

AN XY:

725874

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.0693

Gnomad4 ASJ exome

AF:

0.0642

Gnomad4 EAS exome

AF:

0.0675

Gnomad4 SAS exome

AF:

0.0789

Gnomad4 FIN exome

AF:

0.0996

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0940

AC:

14310

AN:

152162

Hom.:

762

Cov.:

AF XY:

0.0915

AC XY:

6809

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0444

Gnomad4 AMR

AF:

0.0911

Gnomad4 ASJ

AF:

0.0568

Gnomad4 EAS

AF:

0.0624

Gnomad4 SAS

AF:

0.0817

Gnomad4 FIN

AF:

0.0925

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.0823

Alfa

AF:

0.0944

Hom.:

385

Bravo

AF:

0.0898

Asia WGS

AF:

0.0940

AC:

324

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2016

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. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Early myoclonic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.44

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over