11-794837-T-C

Position:

• chr11-794837-T-C

Variant summary

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

The NM_001191061.2(SLC25A22):​c.85A>G​(p.Ile29Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,435,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC25A22 NM_001191061.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.85A>G	p.Ile29Val	missense_variant	3/10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3	c.85A>G	p.Ile29Val	missense_variant	3/10	1	NM_001191061.2	ENSP00000486058.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435882 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 711578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T;T;.;.;.;.;.;.;.;.;T;T;T;.;.;.;.;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	.;.;T;D;T;T;T;T;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.013	D
MutationAssessor	Benign	1.0	L;L;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.83	N;.;N;N;.;N;.;N;N;N;N;N;N;.;N;N;.;N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0020	D;.;D;D;.;D;.;D;D;D;D;D;D;.;D;D;.;D;D
Sift4G	Benign	0.096	T;T;T;T;T;.;T;T;T;.;T;.;.;.;.;.;.;.;.
Polyphen		0.95	P;P;P;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.47
MutPred		0.52		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.41
MPC		0.51
ClinPred		0.59	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.92

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: rs1386206620; hg19: chr11-794837;