Genetic Variant SLC7A3:p.Val210Ile (chrX-70928535-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_032803.6(SLC7A3):c.628G>A(p.Val210Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,204,339 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000018 ( 0 hom. 3 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.861

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.113771915).

BP6

Variant X-70928535-C-T is Benign according to our data. Variant chrX-70928535-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3771600.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A3	NM_032803.6 link	c.628G>A	p.Val210Ile	missense_variant	Exon 4 of 12	ENST00000374299.8	NP_116192.4	Q8WY07
SLC7A3	NM_001048164.3 link	c.628G>A	p.Val210Ile	missense_variant	Exon 4 of 12		NP_001041629.1	Q8WY07
SLC7A3	XM_047442598.1 link	c.628G>A	p.Val210Ile	missense_variant	Exon 3 of 11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8 link	c.628G>A	p.Val210Ile	missense_variant	Exon 4 of 12	1	NM_032803.6	ENSP00000363417.3		Q8WY07
SLC7A3	ENST00000298085.4 link	c.628G>A	p.Val210Ile	missense_variant	Exon 4 of 12	2		ENSP00000298085.4		Q8WY07

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33234

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1093245

Hom.:

Cov.:

AF XY:

0.00000835

AC XY:

AN XY:

359279

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.0000519

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC7A3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.9

DANN

Benign

0.50

DEOGEN2

Benign

0.16

T;T

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.67

.;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.94

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.15

N;N

REVEL

Benign

0.22

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.072

MutPred

0.40

Loss of methylation at K211 (P = 0.0583);Loss of methylation at K211 (P = 0.0583);

MVP

0.28

MPC

0.27

ClinPred

0.56

GERP RS

2.6

Varity_R

0.063

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over