11-794482-C-G

Variant names:

• chr11-794482-C-G
• rs193920962
• NM_001191061.2:c.178G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001191061.2(SLC25A22):​c.178G>C​(p.Glu60Gln) 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. 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: 5.87

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.178G>C	p.Glu60Gln	missense_variant	Exon 4 of 10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3	c.178G>C	p.Glu60Gln	missense_variant	Exon 4 of 10	1	NM_001191061.2	ENSP00000486058.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248052 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;T;.;.;.;.;.;.;.;.;T;T;T;.;.;.;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.64	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.5	M;M;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	D;.;D;D;.;D;.;D;D;D;D;D;D;.;D;D;.;D;.
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0010	D;.;D;D;.;D;.;D;D;D;D;D;D;.;D;D;.;D;.
Sift4G	Uncertain	0.0040	D;D;D;D;D;.;D;D;D;.;D;.;.;.;.;.;.;.;.
Polyphen		1.0	D;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.90
MutPred		0.79		Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);.;Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);
MVP		0.77
MPC		1.1
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.81
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs193920962; hg19: chr11-794482;