X-70926625-G-C

Position:

• chrX-70926625-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032803.6(SLC7A3):​c.1522C>G​(p.Leu508Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,191,787 control chromosomes in the GnomAD database, including 16,800 homozygotes. There are 57,771 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (4487 hom., 8165 hem., cov: 22)
  • Exomes 𝑓: 0.14 (12313 hom. 49606 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.745551E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A3	NM_032803.6	c.1522C>G	p.Leu508Val	missense_variant	10/12	ENST00000374299.8
SLC7A3	NM_001048164.3	c.1522C>G	p.Leu508Val	missense_variant	10/12
SLC7A3	XM_047442598.1	c.1522C>G	p.Leu508Val	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A3	ENST00000374299.8	c.1522C>G	p.Leu508Val	missense_variant	10/12	1	NM_032803.6	P1
SLC7A3	ENST00000298085.4	c.1522C>G	p.Leu508Val	missense_variant	10/12	2		P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 28514 AN: 110244 Hom.: 4481 Cov.: 22 AF XY: 0.250 AC XY: 8126 AN XY: 32546

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.0221

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.0928

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.238 AC: 36218 AN: 151911 Hom.: 5193 AF XY: 0.224 AC XY: 10369 AN XY: 46357

Gnomad AFR exome AF: 0.567

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.350

Gnomad FIN exome AF: 0.0827

Gnomad NFE exome AF: 0.0844

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.137 AC: 148473 AN: 1081492 Hom.: 12313 Cov.: 33 AF XY: 0.141 AC XY: 49606 AN XY: 352210

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.0854

Gnomad4 NFE exome AF: 0.0888

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.259 AC: 28567 AN: 110295 Hom.: 4487 Cov.: 22 AF XY: 0.250 AC XY: 8165 AN XY: 32609

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.251

Alfa AF: 0.131 Hom.: 3702

Bravo AF: 0.301

TwinsUK AF: 0.0974 AC: 361

ALSPAC AF: 0.0921 AC: 266

ESP6500AA AF: 0.565 AC: 2165

ESP6500EA AF: 0.0949 AC: 638

ExAC AF: 0.216 AC: 25798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.62
DANN	Benign	0.16
DEOGEN2	Benign	0.018	T;T
FATHMM_MKL	Benign	0.0080	N
MetaRNN	Benign	0.000057	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.3	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.21
Sift	Benign	0.58	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.0	B;B
Vest4		0.016
MPC		0.33
ClinPred		0.0012	T
GERP RS		4.2
Varity_R		0.055
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs6525447; hg19: chrX-70146475; COSMIC: COSV53227576;