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. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001191061.2(SLC25A22):​c.234C>T​(p.Pro78Pro) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P78P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.094 (762 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11608 hom.)
• Consequence: SLC25A22 NM_001191061.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.35
• Publications: 14 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 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

GnomAD2 exomes AF: 0.0965 AC: 24059 AN: 249224 AF XY: 0.0984

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 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

African (AFR) AF: 0.0394 AC: 1320 AN: 33480

American (AMR) AF: 0.0693 AC: 3098 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 1679 AN: 26136

East Asian (EAS) AF: 0.0675 AC: 2678 AN: 39698

South Asian (SAS) AF: 0.0789 AC: 6803 AN: 86256

European-Finnish (FIN) AF: 0.0996 AC: 5063 AN: 50828

Middle Eastern (MID) AF: 0.0550 AC: 317 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 151063 AN: 1111916

Other (OTH) AF: 0.107 AC: 6466 AN: 60382

GnomAD4 genome AF: 0.0940 AC: 14310 AN: 152162 Hom.: 762 Cov.: 32 AF XY: 0.0915 AC XY: 6809 AN XY: 74386

African (AFR) AF: 0.0444 AC: 1842 AN: 41530

American (AMR) AF: 0.0911 AC: 1393 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.0624 AC: 322 AN: 5162

South Asian (SAS) AF: 0.0817 AC: 393 AN: 4808

European-Finnish (FIN) AF: 0.0925 AC: 981 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8919 AN: 67968

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0908 Hom.: 659

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

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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. -

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
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.44
DANN	Benign	0.89
PhyloP100		-2.4
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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