rs1215087087

Variant names:

• chr11-793587-C-G
• NM_001191061.2:c.235G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-793587-C-G
• chr11-793587-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001191061.2(SLC25A22):​c.235G>C​(p.Glu79Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A22 NM_001191061.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.235G>C	p.Glu79Gln	missense_variant	Exon 5 of 10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3	c.235G>C	p.Glu79Gln	missense_variant	Exon 5 of 10	1	NM_001191061.2	ENSP00000486058.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459454 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726040

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	36
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;T;.;.;.;.;.;.;.;.;T;T;T;.;.;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.75	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.7	L;L;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	D;.;D;D;.;D;.;D;D;D;.;D;D;.;D;D;.
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D;.;D;D;.;D;.;D;D;D;.;D;D;.;D;D;.
Sift4G	Uncertain	0.034	D;D;D;D;T;.;D;D;D;.;D;.;.;.;.;.;.
Polyphen		0.99	D;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.75
MutPred		0.66		Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);.;Gain of methylation at K83 (P = 0.1562);.;Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);
MVP		0.72
MPC		1.2
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.88
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-793587;