11-62856339-T-C

Variant names:

• chr11-62856339-T-C
• rs764761894
• ENST00000377890.6:c.70T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001012662.3(SLC3A2):​c.70T>C​(p.Ser24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: SLC3A2 NM_001012662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0110

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059986234).
• BS2: High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001012662.3	c.70T>C	p.Ser24Pro	missense_variant	Exon 1 of 12		NP_001012680.1
SLC3A2	NM_002394.6	c.70T>C	p.Ser24Pro	missense_variant	Exon 1 of 12		NP_002385.3
SLC3A2	NM_001012664.3	c.70T>C	p.Ser24Pro	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.70T>C	p.Ser24Pro	missense_variant	Exon 1 of 12	1		ENSP00000367122.2
SLC3A2	ENST00000377889.6	c.70T>C	p.Ser24Pro	missense_variant	Exon 1 of 10	1		ENSP00000367121.2
SLC3A2	ENST00000538084.2	c.70T>C	p.Ser24Pro	missense_variant	Exon 1 of 13	3		ENSP00000440001.2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000677 AC: 17 AN: 251118 Hom.: 0 AF XY: 0.0000737 AC XY: 10 AN XY: 135748

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: 0.000261

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1460966 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28 AN XY: 726624

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: 0.000151

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74488

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000245 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70T>C (p.S24P) alteration is located in exon 1 (coding exon 1) of the SLC3A2 gene. This alteration results from a T to C substitution at nucleotide position 70, causing the serine (S) at amino acid position 24 to be replaced by a proline (P). 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	0.061
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;.;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.46	T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.060	T;T;T;T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	0.0	N;.;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.51	N;N;N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.046	D;D;T;D
Polyphen		0.0020	B;.;B;B
Vest4		0.18
MutPred		0.081		Loss of phosphorylation at S24 (P = 0.0436);Loss of phosphorylation at S24 (P = 0.0436);Loss of phosphorylation at S24 (P = 0.0436);Loss of phosphorylation at S24 (P = 0.0436);
MVP		0.25
MPC		1.5
ClinPred		0.18	T
GERP RS		0.069
Varity_R		0.14
gMVP		0.033

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

LitVar

Other links and lift over

dbSNP: rs764761894; hg19: chr11-62623811;