chr3-170480891-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C464G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 6 hom. )

Consequence

SLC7A14
NM_020949.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:2B:4

Conservation

PhyloP100: 5.52

Publications

9 publications found

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:

ENSG00000285218 (HGNC:):

ENSG00000285218 links:

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

SLC7A14-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

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

BP6

Variant 3-170480891-C-A is Benign according to our data. Variant chr3-170480891-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 126448.

BS2

High Homozygotes in GnomAdExome4 at 6 AR,Unknown,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLC7A14	NM_020949.3 link	c.1391G>T	p.Cys464Phe	missense_variant	Exon 7 of 8	ENST00000231706.6	NP_066000.2
SLC7A14-AS1	NR_135555.1 link	n.215+4018C>A		intron_variant	Intron 2 of 2
SLC7A14-AS1	NR_135556.1 link	n.215+4018C>A		intron_variant	Intron 2 of 5
SLC7A14-AS1	NR_135557.1 link	n.221+4018C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A14	ENST00000231706.6 link	c.1391G>T	p.Cys464Phe	missense_variant	Exon 7 of 8	2	NM_020949.3	ENSP00000231706.4
ENSG00000285218	ENST00000486975.1 link	c.391+57564C>A		intron_variant	Intron 2 of 3	2		ENSP00000417434.1

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

GnomAD2 exomes

AF:

0.00103

AC:

260

AN:

251432

AF XY:

0.000949

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 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

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0114

AC:

452

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000629

AC:

AN:

1112012

Other (OTH)

AF:

0.00214

AC:

129

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000532

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41522

American (AMR)

AF:

0.000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0120

AC:

AN:

5156

South Asian (SAS)

AF:

0.000208

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000691

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: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinitis pigmentosa 68

Pathogenic:1Uncertain:2

Apr 05, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Mar 27, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:curation

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

SLC7A14-related disorder

Benign:1

Jul 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

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

(source)

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

PhyloP100

5.5

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

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over