Genetic Variant SLC7A3:p.Leu508Val (chrX-70926625-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032803.6(SLC7A3):c.1522C>G(p.Leu508Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,191,787 control chromosomes in the GnomAD database, including 16,800 homozygotes. There are 57,771 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.26 ( 4487 hom., 8165 hem., cov: 22)

Exomes 𝑓: 0.14 ( 12313 hom. 49606 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.420

Publications

22 publications found

Variant links:

Genes affected

SLC7A3 (HGNC:11061): (solute carrier family 7 member 3) This gene encodes a member of the solute carrier family 7. The encoded protein is a sodium-independent cationic amino acid transporter. Alternate splicing results in multiple transcripts that encoded the same protein.[provided by RefSeq, May 2010]

SLC7A3 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SLC7A3 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=5.745551E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLC7A3	NM_032803.6 link	c.1522C>G	p.Leu508Val	missense_variant	Exon 10 of 12	ENST00000374299.8	NP_116192.4
SLC7A3	NM_001048164.3 link	c.1522C>G	p.Leu508Val	missense_variant	Exon 10 of 12		NP_001041629.1
SLC7A3	XM_047442598.1 link	c.1522C>G	p.Leu508Val	missense_variant	Exon 9 of 11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8 link	c.1522C>G	p.Leu508Val	missense_variant	Exon 10 of 12	1	NM_032803.6	ENSP00000363417.3
SLC7A3	ENST00000298085.4 link	c.1522C>G	p.Leu508Val	missense_variant	Exon 10 of 12	2		ENSP00000298085.4

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

28514

AN:

110244

Hom.:

4481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.0221

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.0928

Gnomad NFE

AF:

0.0877

Gnomad OTH

AF:

0.247

GnomAD2 exomes

AF:

0.238

AC:

36218

AN:

151911

AF XY:

0.224

show subpopulations

Gnomad AFR exome

AF:

0.567

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.0827

Gnomad NFE exome

AF:

0.0844

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.137

AC:

148473

AN:

1081492

Hom.:

12313

Cov.:

AF XY:

0.141

AC XY:

49606

AN XY:

352210

show subpopulations

African (AFR)

AF:

0.572

AC:

14928

AN:

26086

American (AMR)

AF:

0.457

AC:

14821

AN:

32446

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

2035

AN:

19049

East Asian (EAS)

AF:

0.453

AC:

13416

AN:

29648

South Asian (SAS)

AF:

0.342

AC:

17635

AN:

51618

European-Finnish (FIN)

AF:

0.0854

AC:

3381

AN:

39571

Middle Eastern (MID)

AF:

0.122

AC:

480

AN:

3928

European-Non Finnish (NFE)

AF:

0.0888

AC:

74033

AN:

833588

Other (OTH)

AF:

0.170

AC:

7744

AN:

45558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4184

8368

12551

16735

20919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3394

6788

10182

13576

16970

<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:

0.259

AC:

28567

AN:

110295

Hom.:

4487

Cov.:

AF XY:

0.250

AC XY:

8165

AN XY:

32609

show subpopulations

African (AFR)

AF:

0.555

AC:

16694

AN:

30092

American (AMR)

AF:

0.354

AC:

3648

AN:

10298

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

267

AN:

2634

East Asian (EAS)

AF:

0.450

AC:

1551

AN:

3443

South Asian (SAS)

AF:

0.348

AC:

886

AN:

2544

European-Finnish (FIN)

AF:

0.0779

AC:

459

AN:

5894

Middle Eastern (MID)

AF:

0.0926

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0877

AC:

4648

AN:

52985

Other (OTH)

AF:

0.251

AC:

379

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

599

1197

1796

2394

2993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.131

Hom.:

3702

Bravo

AF:

0.301

TwinsUK

AF:

0.0974

AC:

361

ALSPAC

AF:

0.0921

AC:

266

ESP6500AA

AF:

0.565

AC:

2165

ESP6500EA

AF:

0.0949

AC:

638

ExAC

AF:

0.216

AC:

25798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.62

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.018

T;T

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.0

.;T

MetaRNN

Benign

0.000057

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.3

N;N

PhyloP100

-0.42

PrimateAI

Benign

0.38

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.21

Sift

Benign

0.58

T;T

Sift4G

Benign

0.62

T;T

Vest4

0.016

ClinPred

0.0012

GERP RS

4.2

Varity_R

0.055

gMVP

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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