Genetic Variant NM_032803.6:c.845G>T (chrX-70927996-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032803.6(SLC7A3):c.845G>T(p.Arg282Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,954 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. R282H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A3	NM_032803.6 link	c.845G>T	p.Arg282Leu	missense_variant	Exon 6 of 12	ENST00000374299.8	NP_116192.4	Q8WY07
SLC7A3	NM_001048164.3 link	c.845G>T	p.Arg282Leu	missense_variant	Exon 6 of 12		NP_001041629.1	Q8WY07
SLC7A3	XM_047442598.1 link	c.845G>T	p.Arg282Leu	missense_variant	Exon 5 of 11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8 link	c.845G>T	p.Arg282Leu	missense_variant	Exon 6 of 12	1	NM_032803.6	ENSP00000363417.3		Q8WY07
SLC7A3	ENST00000298085.4 link	c.845G>T	p.Arg282Leu	missense_variant	Exon 6 of 12	2		ENSP00000298085.4		Q8WY07

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097954

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363312

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

D;D

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.86

.;D

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

4.0

H;H

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.86

P;P

Vest4

0.53

MutPred

0.58

Loss of disorder (P = 0.037);Loss of disorder (P = 0.037);

MVP

0.87

MPC

0.66

ClinPred

0.99

GERP RS

0.47

Varity_R

0.80

gMVP

0.91

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over