11-62881138-A-G

Variant names:

• chr11-62881138-A-G
• NM_001013251.3:c.115A>G

Variant summary

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

The NM_001013251.3(SLC3A2):​c.115A>G​(p.Lys39Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.85

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.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001013251.3	c.115A>G	p.Lys39Glu	missense_variant	Exon 1 of 9	ENST00000338663.12	NP_001013269.1
SLC3A2	NM_001012662.3	c.421A>G	p.Lys141Glu	missense_variant	Exon 4 of 12		NP_001012680.1
SLC3A2	NM_002394.6	c.418A>G	p.Lys140Glu	missense_variant	Exon 4 of 12		NP_002385.3
SLC3A2	NM_001012664.3	c.232A>G	p.Lys78Glu	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.115A>G	p.Lys39Glu	missense_variant	Exon 1 of 9	1	NM_001013251.3	ENSP00000340815.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452040 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721424

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: 9.02e-7

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

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.421A>G (p.K141E) alteration is located in exon 4 (coding exon 4) of the SLC3A2 gene. This alteration results from a A to G substitution at nucleotide position 421, causing the lysine (K) at amino acid position 141 to be replaced by a glutamic acid (E). 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	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;.;.;.;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D;D;D;D;T;D;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.8	L;.;.;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.047	D;D;T;T;T;T;T
Sift4G	Benign	0.086	T;T;T;T;D;T;D
Polyphen		0.97	D;.;D;D;.;D;.
Vest4		0.53
MutPred		0.19		Loss of ubiquitination at K140 (P = 0.0034);.;.;.;.;.;.;
MVP		0.84
MPC		1.7
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.47
gMVP		0.68

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: chr11-62648610;