rs369735050

chr11-793538-G-Achr11-793538-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001191061.2(SLC25A22):c.284C>T(p.Ser95Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S95C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A22 NM_001191061.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A22	NM_001191061.2	c.284C>T	p.Ser95Phe	missense_variant	5/10	ENST00000628067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A22	ENST00000628067.3	c.284C>T	p.Ser95Phe	missense_variant	5/10	1	NM_001191061.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Benign	0.27	T;T;T;.;.;.;.;.;.;.;.;T;T;T;.;.;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.2	L;L;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.0	D;.;D;D;.;D;.;D;D;D;.;D;D;.;D;D;.
REVEL	Uncertain	0.50
Sift	Benign	0.33	T;.;T;T;.;T;.;T;T;T;.;T;T;.;T;T;.
Sift4G	Benign	0.21	T;T;T;T;T;.;T;T;T;.;T;.;.;.;.;.;.
Polyphen		0.0060	B;B;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.80
MutPred		0.45		Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);.;Loss of disorder (P = 0.0109);.;Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);
MVP		0.70
MPC		1.2
ClinPred		0.95	D
GERP RS		3.5
Varity_R		0.47
gMVP		0.94

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: rs369735050; hg19: chr11-793538;