X-70926950-C-T

Position:

• chrX-70926950-C-T

Variant summary

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

The NM_032803.6(SLC7A3):​c.1378G>A​(p.Gly460Arg) 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 1,097,819 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.484

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6	c.1378G>A	p.Gly460Arg	missense_variant	9/12	ENST00000374299.8	NP_116192.4
SLC7A3	NM_001048164.3	c.1378G>A	p.Gly460Arg	missense_variant	9/12		NP_001041629.1
SLC7A3	XM_047442598.1	c.1378G>A	p.Gly460Arg	missense_variant	8/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8	c.1378G>A	p.Gly460Arg	missense_variant	9/12	1	NM_032803.6	ENSP00000363417.3
SLC7A3	ENST00000298085.4	c.1378G>A	p.Gly460Arg	missense_variant	9/12	2		ENSP00000298085.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097819 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363177

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.: 23

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

Oct 29, 2024

The c.1378G>A (p.G460R) alteration is located in exon 9 (coding exon 8) of the SLC7A3 gene. This alteration results from a G to A substitution at nucleotide position 1378, causing the glycine (G) at amino acid position 460 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.79
DANN	Benign	0.44
DEOGEN2	Benign	0.038	T;T
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.22	.;T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N;N
REVEL	Benign	0.27
Sift	Benign	0.12	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0010	B;B
Vest4		0.41
MutPred		0.68		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.46
MPC		0.40
ClinPred		0.057	T
GERP RS		2.4
Varity_R		0.063
gMVP		0.61

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-70146800;