rs79668755

chr3-170480891-C-Achr3-170480891-C-Gchr3-170480891-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020949.3(SLC7A14):c.1391G>T(p.Cys464Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000423 in 1,614,074 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00053 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: SLC7A14 NM_020949.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 U:1 B:3
• Conservation: PhyloP100: 5.52

Genes affected

SLC7A14 (HGNC:29326): (solute carrier family 7 member 14) This gene is predicted to encode a glycosylated, cationic amino acid transporter protein with 14 transmembrane domains. This gene is primarily expressed in skin fibroblasts, neural tissue, and primary endothelial cells and its protein is predicted to mediate lysosomal uptake of cationic amino acids. Mutations in this gene are associated with autosomal recessive retinitis pigmentosa. In mice, this gene is expressed in the photoreceptor layer of the retina where its expression increases over the course of retinal development and persists in the mature retina. [provided by RefSeq, Apr 2014]

SLC7A14-AS1 (HGNC:54092): (SLC7A14 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011369795).
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A14	NM_020949.3	c.1391G>T	p.Cys464Phe	missense_variant	7/8	ENST00000231706.6
SLC7A14-AS1	NR_135556.1	n.215+4018C>A		intron_variant, non_coding_transcript_variant
SLC7A14-AS1	NR_135555.1	n.215+4018C>A		intron_variant, non_coding_transcript_variant
SLC7A14-AS1	NR_135557.1	n.221+4018C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A14	ENST00000231706.6	c.1391G>T	p.Cys464Phe	missense_variant	7/8	2	NM_020949.3	P1
SLC7A14-AS1	ENST00000644993.1	n.142+4018C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000533 AC: 81 AN: 152062 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00103 AC: 260 AN: 251432 Hom.: 4 AF XY: 0.000949 AC XY: 129 AN XY: 135890

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0134

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000411 AC: 601 AN: 1461894 Hom.: 6 Cov.: 30 AF XY: 0.000395 AC XY: 287 AN XY: 727248

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0114

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00214

GnomAD4 genome AF: 0.000532 AC: 81 AN: 152180 Hom.: 1 Cov.: 32 AF XY: 0.000538 AC XY: 40 AN XY: 74402

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000795 Hom.: 4

Bravo AF: 0.000552

ExAC AF: 0.000972 AC: 118

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Uncertain:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Retinitis pigmentosa 68 Pathogenic:1 Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 27, 2014	- -
Uncertain significance, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NM_020949.2:c.1391G>T in the SLC7A14 gene has an allele frequency of 0.013 in East Asian subpopulation in the gnomAD database. It has been reported previously in individuals with retinitis pigmentosa, including one homozygous and one compound heterozygote (PMID: 24670872). We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PM3, BS1. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

SLC7A14-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
Cadd	Benign	18
Dann	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.86	N
REVEL	Pathogenic	0.79
Sift	Benign	0.67	T
Sift4G	Benign	0.68	T
Polyphen		0.40	B
Vest4		0.88
MVP		0.62
MPC		0.22
ClinPred		0.019	T
GERP RS		5.0
Varity_R		0.34
gMVP		0.60

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: rs79668755; hg19: chr3-170198680; COSMIC: COSV51586728;