X-70927322-G-C

Position:

• chrX-70927322-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032803.6(SLC7A3):​c.1246C>G​(p.Leu416Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 4.84

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6	c.1246C>G	p.Leu416Val	missense_variant	8/12	ENST00000374299.8	NP_116192.4
SLC7A3	NM_001048164.3	c.1246C>G	p.Leu416Val	missense_variant	8/12		NP_001041629.1
SLC7A3	XM_047442598.1	c.1246C>G	p.Leu416Val	missense_variant	7/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8	c.1246C>G	p.Leu416Val	missense_variant	8/12	1	NM_032803.6	ENSP00000363417.3
SLC7A3	ENST00000298085.4	c.1246C>G	p.Leu416Val	missense_variant	8/12	2		ENSP00000298085.4

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2024

The c.1246C>G (p.L416V) alteration is located in exon 8 (coding exon 7) of the SLC7A3 gene. This alteration results from a C to G substitution at nucleotide position 1246, causing the leucine (L) at amino acid position 416 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;D
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	.;T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.98	D;D
Vest4		0.69
MutPred		0.51		Gain of catalytic residue at L416 (P = 0.0953);Gain of catalytic residue at L416 (P = 0.0953);
MVP		0.97
MPC		1.0
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.92
gMVP		0.79

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-70147172;