Genetic Variant NM_032803.6:c.1798C>A (chrX-70925875-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032803.6(SLC7A3):c.1798C>A(p.Arg600Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R600C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.749

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03874138).

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.1798C>A	p.Arg600Ser	missense	Exon 12 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.1798C>A	p.Arg600Ser	missense	Exon 12 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.1798C>A	p.Arg600Ser	missense	Exon 12 of 12	ENSP00000363417.3	Q8WY07
SLC7A3	ENST00000921007.1		c.1849C>A	p.Arg617Ser	missense	Exon 13 of 13	ENSP00000591066.1
SLC7A3	ENST00000921008.1		c.1849C>A	p.Arg617Ser	missense	Exon 13 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000182

AC:

AN:

1097915

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363271

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841838

Other (OTH)

AF:

0.00

AC:

AN:

46085

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.22

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.41

M_CAP

Benign

0.056

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.0

PhyloP100

0.75

PrimateAI

Benign

0.22

PROVEAN

Benign

1.6

REVEL

Benign

0.19

Sift

Benign

0.73

Sift4G

Benign

0.73

Polyphen

0.0

Vest4

0.063

MutPred

0.30

Loss of catalytic residue at R600 (P = 0.0099)

MVP

0.25

MPC

0.37

ClinPred

0.018

GERP RS

-0.28

Varity_R

0.083

gMVP

0.20

Mutation Taster

=97/3

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over