rs80335370

Variant names:

• chr11-793588-G-A
• rs80335370
• NM_001191061.2:c.234C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-793588-G-A
• chr11-793588-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001425344.1(SLC25A22):​c.-85C>T variant causes a 5 prime UTR premature start codon gain 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_001425344.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.35

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]

ACMG classification

Verdict is Benign. Variant got -18 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.
• 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 rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.234C>T	p.Pro78Pro	synonymous_variant	Exon 5 of 10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3	c.234C>T	p.Pro78Pro	synonymous_variant	Exon 5 of 10	1	NM_001191061.2	ENSP00000486058.1

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14308 AN: 152044 Hom.: 763 Cov.: 32

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

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.: 32 AF XY: 0.121 AC XY: 87839 AN XY: 725874

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.: 32 AF XY: 0.0915 AC XY: 6809 AN XY: 74386

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

Submissions by phenotype

not provided Benign:3

May 07, 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

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jan 18, 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. -

Early infantile epileptic encephalopathy with suppression bursts 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
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

Other links and lift over

dbSNP: rs80335370; hg19: chr11-793588; COSMIC: COSV57192934; COSMIC: COSV57192934;