11-792400-G-T

Position:

• chr11-792400-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001191061.2(SLC25A22):​c.646C>A​(p.Arg216Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A22 NM_001191061.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1480757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.646C>A	p.Arg216Ser	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.646C>A	p.Arg216Ser	missense_variant	8/10	1	NM_001191061.2	ENSP00000486058.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	0.0036	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.023	T;T;T;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.86	.;.;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L;L;L;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.76	N;.;N;N;.
REVEL	Benign	0.26
Sift	Benign	0.69	T;.;T;T;.
Sift4G	Benign	0.69	T;T;T;T;T
Polyphen		0.13	B;B;B;.;.
Vest4		0.43
MutPred		0.45		Gain of glycosylation at R216 (P = 0.0454);Gain of glycosylation at R216 (P = 0.0454);Gain of glycosylation at R216 (P = 0.0454);.;Gain of glycosylation at R216 (P = 0.0454);
MVP		0.57
MPC		0.51
ClinPred		0.24	T
GERP RS		2.9
Varity_R		0.21
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs771544252; hg19: chr11-792400;