8-17561952-G-A

Variant names:

• chr8-17561952-G-A
• rs56335308
• NM_001370338.1:c.1513G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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: 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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370338.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	NM_001370338.1	MANE Select	c.1513G>A	p.Val505Met	missense	Exon 11 of 13	NP_001357267.1	P52569-1
	SLC7A2	NM_001164771.2		c.1633G>A	p.Val545Met	missense	Exon 10 of 12	NP_001158243.1	P52569-3
	SLC7A2	NM_003046.6		c.1630G>A	p.Val544Met	missense	Exon 10 of 12	NP_003037.4	P52569-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	ENST00000494857.6	TSL:5 MANE Select	c.1513G>A	p.Val505Met	missense	Exon 11 of 13	ENSP00000419140.2	P52569-1
	SLC7A2	ENST00000004531.14	TSL:1	c.1633G>A	p.Val545Met	missense	Exon 10 of 12	ENSP00000004531.10	P52569-3
	SLC7A2	ENST00000398090.3	TSL:1	c.1630G>A	p.Val544Met	missense	Exon 10 of 12	ENSP00000381164.3	P52569-2

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

GnomAD2 exomes AF: 0.0182 AC: 4563 AN: 251204 AF XY: 0.0188

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 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

African (AFR) AF: 0.00828 AC: 277 AN: 33472

American (AMR) AF: 0.00955 AC: 427 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 335 AN: 26134

East Asian (EAS) AF: 0.0528 AC: 2096 AN: 39688

South Asian (SAS) AF: 0.0191 AC: 1648 AN: 86246

European-Finnish (FIN) AF: 0.00986 AC: 526 AN: 53360

Middle Eastern (MID) AF: 0.0331 AC: 191 AN: 5764

European-Non Finnish (NFE) AF: 0.0257 AC: 28540 AN: 1111812

Other (OTH) AF: 0.0248 AC: 1499 AN: 60388

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

African (AFR) AF: 0.0101 AC: 419 AN: 41572

American (AMR) AF: 0.0143 AC: 219 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.0318 AC: 164 AN: 5160

South Asian (SAS) AF: 0.0183 AC: 88 AN: 4818

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1486 AN: 68030

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0215 Hom.: 141

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 v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.64
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.33
Sift	Benign	0.13	T
Sift4G	Benign	0.077	T
Polyphen		0.50	P
Vest4		0.24
MPC		0.026
ClinPred		0.0090	T
GERP RS		-3.6
Varity_R		0.029
gMVP		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56335308; hg19: chr8-17419461;