3-170480891-C-A

Position:

chr3-170480891-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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 Benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 6 hom. )

Consequence

SLC7A14
NM_020949.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1U:1B:4

Conservation

PhyloP100: 5.52

Variant links:

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 links:

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

SLC7A14-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011369795).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC7A14	NM_020949.3 linkuse as main transcript	c.1391G>T	p.Cys464Phe	missense_variant	7/8	ENST00000231706.6	NP_066000.2
SLC7A14-AS1	NR_135556.1 linkuse as main transcript	n.215+4018C>A		intron_variant, non_coding_transcript_variant
SLC7A14-AS1	NR_135555.1 linkuse as main transcript	n.215+4018C>A		intron_variant, non_coding_transcript_variant
SLC7A14-AS1	NR_135557.1 linkuse as main transcript	n.221+4018C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A14	ENST00000231706.6 linkuse as main transcript	c.1391G>T	p.Cys464Phe	missense_variant	7/8	2	NM_020949.3	ENSP00000231706	P1
SLC7A14-AS1	ENST00000644993.1 linkuse as main transcript	n.142+4018C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000949

AC XY:

129

AN XY:

135890

show subpopulations

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.:

Cov.:

AF XY:

0.000395

AC XY:

287

AN XY:

727248

show subpopulations

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:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74402

show subpopulations

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.:

Bravo

AF:

0.000552

ExAC

AF:

0.000972

AC:

118

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 68

Pathogenic:1Uncertain: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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

SLC7A14-related disorder

Benign:1

Likely benign, no assertion criteria provided

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

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.024

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.86

REVEL

Pathogenic

0.79

Sift

Benign

0.67

Sift4G

Benign

0.68

Polyphen

0.40

Vest4

0.88

MVP

0.62

MPC

0.22

ClinPred

0.019

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over