chrX-70927493-T-C

Position:

• chrX-70927493-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032803.6(SLC7A3):​c.1174A>G​(p.Ile392Val) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.08

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039808184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6	c.1174A>G	p.Ile392Val	missense_variant	7/12	ENST00000374299.8	NP_116192.4
SLC7A3	NM_001048164.3	c.1174A>G	p.Ile392Val	missense_variant	7/12		NP_001041629.1
SLC7A3	XM_047442598.1	c.1174A>G	p.Ile392Val	missense_variant	6/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8	c.1174A>G	p.Ile392Val	missense_variant	7/12	1	NM_032803.6	ENSP00000363417.3
SLC7A3	ENST00000298085.4	c.1174A>G	p.Ile392Val	missense_variant	7/12	2		ENSP00000298085.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC7A3-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 07, 2024

The SLC7A3 c.1174A>G variant is predicted to result in the amino acid substitution p.Ile392Val. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.1
DANN	Benign	0.44
DEOGEN2	Benign	0.16	T;T
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.74	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.010	N;N
REVEL	Benign	0.11
Sift	Benign	0.71	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.0010	B;B
Vest4		0.097
MutPred		0.40		Gain of catalytic residue at I392 (P = 0.028);Gain of catalytic residue at I392 (P = 0.028);
MVP		0.25
MPC		0.28
ClinPred		0.023	T
GERP RS		-6.1
Varity_R		0.045
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70147343;