rs121918335

Positions:

• chr11-792340-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001191061.2(SLC25A22):​c.706G>T​(p.Gly236Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A22 NM_001191061.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.91

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994
• PP5: Variant 11-792340-C-A is Pathogenic according to our data. Variant chr11-792340-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 1776.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.706G>T	p.Gly236Trp	missense_variant	8/10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3	c.706G>T	p.Gly236Trp	missense_variant	8/10	1	NM_001191061.2	ENSP00000486058	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental and epileptic encephalopathy, 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D;D;D;.;.
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	.;.;D;D;D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	4.6	H;H;H;.;.
MutationTaster	Benign	1.0	A;A
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.8	D;.;D;.;.
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0090	D;.;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.97
MutPred		0.95		Loss of glycosylation at S237 (P = 0.131);Loss of glycosylation at S237 (P = 0.131);Loss of glycosylation at S237 (P = 0.131);.;Loss of glycosylation at S237 (P = 0.131);
MVP		0.96
MPC		1.3
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.92
gMVP		0.93

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: rs121918335; hg19: chr11-792340;