NM_001191061.2:c.495C>G

Variant names:

• chr11-792645-G-C
• rs374780430
• NM_001191061.2:c.495C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001191061.2(SLC25A22):​c.495C>G​(p.Ala165Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,428,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A165A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC25A22 NM_001191061.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	NM_001191061.2	MANE Select	c.495C>G	p.Ala165Ala	synonymous	Exon 7 of 10	NP_001177990.1
	SLC25A22	NM_001425334.1		c.570C>G	p.Ala190Ala	synonymous	Exon 7 of 10	NP_001412263.1
	SLC25A22	NM_001425335.1		c.534C>G	p.Ala178Ala	synonymous	Exon 7 of 10	NP_001412264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.495C>G	p.Ala165Ala	synonymous	Exon 7 of 10	ENSP00000486058.1
	SLC25A22	ENST00000320230.9	TSL:1	c.495C>G	p.Ala165Ala	synonymous	Exon 7 of 10	ENSP00000322020.5
	SLC25A22	ENST00000531214.5	TSL:2	c.495C>G	p.Ala165Ala	synonymous	Exon 7 of 10	ENSP00000437236.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1428838 Hom.: 0 Cov.: 32 AF XY: 0.00000282 AC XY: 2 AN XY: 708720

African (AFR) AF: 0.00 AC: 0 AN: 32956

American (AMR) AF: 0.00 AC: 0 AN: 40082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 38266

South Asian (SAS) AF: 0.00 AC: 0 AN: 83502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1097288

Other (OTH) AF: 0.0000169 AC: 1 AN: 59214

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.55
PhyloP100		-1.2

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: rs374780430; hg19: chr11-792645;