Genetic Variant SLC7A3:p.Leu326Arg (chrX-70927864-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032803.6(SLC7A3):c.977T>G(p.Leu326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,087,557 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. 3 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Publications

0 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:

ENSG00000295939 (HGNC:):

ENSG00000295939 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18537918).

BS2

High Hemizygotes in GnomAdExome4 at 3 AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032803.6. 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
	SLC7A3	NM_032803.6	MANE Select	c.977T>G	p.Leu326Arg	missense	Exon 6 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.977T>G	p.Leu326Arg	missense	Exon 6 of 12	NP_001041629.1	Q8WY07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A3	ENST00000374299.8	TSL:1 MANE Select	c.977T>G	p.Leu326Arg	missense	Exon 6 of 12	ENSP00000363417.3	Q8WY07
SLC7A3	ENST00000921007.1		c.977T>G	p.Leu326Arg	missense	Exon 6 of 13	ENSP00000591066.1
SLC7A3	ENST00000921008.1		c.977T>G	p.Leu326Arg	missense	Exon 6 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1087557

Hom.:

Cov.:

AF XY:

0.00000843

AC XY:

AN XY:

355723

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26266

American (AMR)

AF:

0.00

AC:

AN:

33391

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19114

East Asian (EAS)

AF:

0.00

AC:

AN:

29924

South Asian (SAS)

AF:

0.00

AC:

AN:

52334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39857

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.00000239

AC:

AN:

836727

Other (OTH)

AF:

0.0000218

AC:

AN:

45820

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.83

M_CAP

Benign

0.073

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.0

PhyloP100

1.8

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.31

Sift

Benign

0.51

Sift4G

Benign

0.52

Polyphen

0.0050

Vest4

0.43

MutPred

0.36

Loss of stability (P = 0.0459)

MVP

0.66

MPC

1.2

ClinPred

0.14

GERP RS

1.1

Varity_R

0.32

gMVP

0.42

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over