dbSNP rs56335308: SLC7A2:p.Val505Met (chr8-17561952-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.636

Publications

13 publications found

Variant links:

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]

SLC7A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A2	NM_001370338.1 link	c.1513G>A	p.Val505Met	missense_variant	Exon 11 of 13	ENST00000494857.6	NP_001357267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A2	ENST00000494857.6 link	c.1513G>A	p.Val505Met	missense_variant	Exon 11 of 13	5	NM_001370338.1	ENSP00000419140.2		P52569-1

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2524

AN:

152162

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0243

AC XY:

17671

AN XY:

727102

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

1664

3328

4993

6657

8321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1140

2280

3420

4560

5700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0166

AC:

2522

AN:

152282

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1203

AN XY:

74460

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.0318

AC:

164

AN:

5160

South Asian (SAS)

AF:

0.0183

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00603

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0218

AC:

1486

AN:

68030

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

131

263

394

526

657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0215

Hom.:

141

Bravo

AF:

0.0172

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.0259

AC:

223

ExAC

AF:

0.0184

AC:

2230

Asia WGS

AF:

0.0250

AC:

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

BayesDel_noAF

Benign

-0.29

CADD

Benign

8.5

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.14

T;T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.76

.;T;.;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.2

M;M;.;.;.;.

PhyloP100

0.64

PrimateAI

Benign

0.29

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

GERP RS

-3.6

Varity_R

0.029

gMVP

0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over