X-70928520-G-A

Position:

• chrX-70928520-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032803.6(SLC7A3):​c.643C>T​(p.His215Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.669

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23443437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A3	NM_032803.6	c.643C>T	p.His215Tyr	missense_variant	4/12	ENST00000374299.8
SLC7A3	NM_001048164.3	c.643C>T	p.His215Tyr	missense_variant	4/12
SLC7A3	XM_047442598.1	c.643C>T	p.His215Tyr	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A3	ENST00000374299.8	c.643C>T	p.His215Tyr	missense_variant	4/12	1	NM_032803.6	P1
SLC7A3	ENST00000298085.4	c.643C>T	p.His215Tyr	missense_variant	4/12	2		P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC7A3-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 24, 2023

The SLC7A3 c.643C>T variant is predicted to result in the amino acid substitution p.His215Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), 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	0.088
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;D
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.87	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.28
Sift	Benign	0.057	T;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.0050	B;B
Vest4		0.21
MutPred		0.35		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.67
MPC		1.0
ClinPred		0.94	D
GERP RS		0.82
Varity_R		0.27
gMVP		0.47

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-70148370;