rs56335308

Positions:

• chr8-17561952-G-A
• chr8-17561952-G-C
• chr8-17561952-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370338.1(SLC7A2):​c.1513G>A​(p.Val505Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,613,864 control chromosomes in the GnomAD database, including 565 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.017 (27 hom., cov: 32)
  • Exomes 𝑓: 0.024 (538 hom.)
• Consequence: SLC7A2 NM_001370338.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041761994).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A2	NM_001370338.1	c.1513G>A	p.Val505Met	missense_variant	11/13	ENST00000494857.6	NP_001357267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A2	ENST00000494857.6	c.1513G>A	p.Val505Met	missense_variant	11/13	5	NM_001370338.1	ENSP00000419140.2

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2524 AN: 152162 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0182 AC: 4563 AN: 251204 Hom.: 54 AF XY: 0.0188 AC XY: 2549 AN XY: 135764

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.00908

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.0318

Gnomad SAS exome AF: 0.0183

Gnomad FIN exome AF: 0.00898

Gnomad NFE exome AF: 0.0222

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.0243 AC: 35539 AN: 1461582 Hom.: 538 Cov.: 31 AF XY: 0.0243 AC XY: 17671 AN XY: 727102

Gnomad4 AFR exome AF: 0.00828

Gnomad4 AMR exome AF: 0.00955

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.00986

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.0166 AC: 2522 AN: 152282 Hom.: 27 Cov.: 32 AF XY: 0.0162 AC XY: 1203 AN XY: 74460

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0183

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.0218

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0222 Hom.: 65

Bravo AF: 0.0172

TwinsUK AF: 0.0232 AC: 86

ALSPAC AF: 0.0218 AC: 84

ESP6500AA AF: 0.00931 AC: 41

ESP6500EA AF: 0.0259 AC: 223

ExAC AF: 0.0184 AC: 2230

Asia WGS AF: 0.0250 AC: 85 AN: 3478

EpiCase AF: 0.0251

EpiControl AF: 0.0209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	8.5
DANN	Benign	0.90
DEOGEN2	Benign	0.14	T;T;.;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.76	.;T;.;T;T;T
MetaRNN	Benign	0.0042	T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.2	M;M;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;N;N;N;.
REVEL	Uncertain	0.33
Sift	Benign	0.13	T;T;T;T;T;.
Sift4G	Benign	0.077	T;T;T;T;T;.
Polyphen		0.50	P;P;B;B;B;.
Vest4		0.24
MPC		0.026
ClinPred		0.0090	T
GERP RS		-3.6
Varity_R		0.029
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56335308; hg19: chr8-17419461;