11-62856275-G-T

Variant names:

• chr11-62856275-G-T
• ENST00000377890.6:c.6G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001012662.3(SLC3A2):​c.6G>T​(p.Glu2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Synonymous variant affecting the same amino acid position (i.e. E2E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC3A2 NM_001012662.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity 4F2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06886539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001012662.3	c.6G>T	p.Glu2Asp	missense_variant	Exon 1 of 12		NP_001012680.1
SLC3A2	NM_002394.6	c.6G>T	p.Glu2Asp	missense_variant	Exon 1 of 12		NP_002385.3
SLC3A2	NM_001012664.3	c.6G>T	p.Glu2Asp	missense_variant	Exon 1 of 10		NP_001012682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000377890.6	c.6G>T	p.Glu2Asp	missense_variant	Exon 1 of 12	1		ENSP00000367122.2
SLC3A2	ENST00000377889.6	c.6G>T	p.Glu2Asp	missense_variant	Exon 1 of 10	1		ENSP00000367121.2
SLC3A2	ENST00000538084.2	c.6G>T	p.Glu2Asp	missense_variant	Exon 1 of 13	3		ENSP00000440001.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458672 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725086

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: 0.00000180

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	0.084
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.087
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T;.;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.43	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	0.0	N;.;N;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.12	N;N;N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;T;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.13
MutPred		0.18		Loss of glycosylation at P5 (P = 0.1313);Loss of glycosylation at P5 (P = 0.1313);Loss of glycosylation at P5 (P = 0.1313);Loss of glycosylation at P5 (P = 0.1313);
MVP		0.49
MPC		0.45
ClinPred		0.14	T
GERP RS		-8.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
gMVP		0.026

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62623747;