11-62881077-G-C

Variant names:

• chr11-62881077-G-C
• NM_001013251.3:c.54G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013251.3(SLC3A2):​c.54G>C​(p.Glu18Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,710 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063649684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001013251.3	c.54G>C	p.Glu18Asp	missense_variant	Exon 1 of 9	ENST00000338663.12	NP_001013269.1
SLC3A2	NM_001012662.3	c.360G>C	p.Glu120Asp	missense_variant	Exon 4 of 12		NP_001012680.1
SLC3A2	NM_002394.6	c.357G>C	p.Glu119Asp	missense_variant	Exon 4 of 12		NP_002385.3
SLC3A2	NM_001012664.3	c.171G>C	p.Glu57Asp	missense_variant	Exon 2 of 10		NP_001012682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12	c.54G>C	p.Glu18Asp	missense_variant	Exon 1 of 9	1	NM_001013251.3	ENSP00000340815.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455710 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 723390

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.360G>C (p.E120D) alteration is located in exon 4 (coding exon 4) of the SLC3A2 gene. This alteration results from a G to C substitution at nucleotide position 360, causing the glutamic acid (E) at amino acid position 120 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.1
DANN	Benign	0.93
DEOGEN2	Benign	0.21	T;.;.;.;.;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.84	T;T;T;T;D;T;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.064	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	N;.;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.43	N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.48	T;T;T;T;T;T;T
Sift4G	Benign	0.69	T;T;T;T;T;T;T
Polyphen		0.014	B;.;B;B;.;B;.
Vest4		0.16
MutPred		0.092		Gain of sheet (P = 0.0073);.;.;.;.;.;.;
MVP		0.50
MPC		0.57
ClinPred		0.26	T
GERP RS		-4.3
Varity_R		0.064
gMVP		0.098

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: chr11-62648549;