rs7944051

chr11-62888346-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001013251.3(SLC3A2):c.1243C>T(p.Pro415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,613,958 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (7 hom.)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.178

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050282776).
• BP6: Variant 11-62888346-C-T is Benign according to our data. Variant chr11-62888346-C-T is described in ClinVar as [Benign]. Clinvar id is 789487.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 597 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A2	NM_001013251.3	c.1243C>T	p.Pro415Ser	missense_variant	9/9	ENST00000338663.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A2	ENST00000338663.12	c.1243C>T	p.Pro415Ser	missense_variant	9/9	1	NM_001013251.3	P2

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 597 AN: 152186 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00103 AC: 258 AN: 250722 Hom.: 0 AF XY: 0.000738 AC XY: 100 AN XY: 135522

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000454 AC: 664 AN: 1461654 Hom.: 7 Cov.: 31 AF XY: 0.000419 AC XY: 305 AN XY: 727118

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.00394 AC: 600 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00367 AC XY: 273 AN XY: 74478

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00102 Hom.: 3

Bravo AF: 0.00458

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.15
Cadd	Benign	13
Dann	Benign	0.91
DEOGEN2	Benign	0.33	T;.;.;.;.;.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.77	T;T;T;T;T;T;T
MetaRNN	Benign	0.0050	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N;N;N;D;D
REVEL	Benign	0.24
Sift	Benign	0.32	T;T;T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T;T;T
Polyphen		0.018	B;.;B;B;B;.;.
Vest4		0.072
MVP		0.69
MPC		0.54
ClinPred		0.0079	T
GERP RS		3.7
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.9
Varity_R		0.14
gMVP		0.22

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: rs7944051; hg19: chr11-62655818;