3-170467074-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020949.3(SLC7A14):c.2297T>C(p.Leu766Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000739 in 1,611,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SLC7A14
NM_020949.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.45

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35030657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A14	NM_020949.3 link	c.2297T>C	p.Leu766Ser	missense_variant	Exon 8 of 8	ENST00000231706.6	NP_066000.2	Q8TBB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC7A14	ENST00000231706.6 link	c.2297T>C	p.Leu766Ser	missense_variant	Exon 8 of 8	2	NM_020949.3	ENSP00000231706.4	Q8TBB6
ENSG00000285218	ENST00000486975.1 link	c.391+43747A>G		intron_variant	Intron 2 of 3	2		ENSP00000417434.1	B4DFI2
ENSG00000285218	ENST00000471373.5 link	n.372+6662A>G		intron_variant	Intron 3 of 3	4
SLC7A14-AS1	ENST00000643719.1 link	n.273+6662A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

248748

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

134432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000733

AC:

107

AN:

1459054

Hom.:

Cov.:

AF XY:

0.0000772

AC XY:

AN XY:

725592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2297T>C (p.L766S) alteration is located in exon 8 (coding exon 7) of the SLC7A14 gene. This alteration results from a T to C substitution at nucleotide position 2297, causing the leucine (L) at amino acid position 766 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Nov 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 766 of the SLC7A14 protein (p.Leu766Ser). This variant is present in population databases (rs200480471, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SLC7A14-related conditions. ClinVar contains an entry for this variant (Variation ID: 963878). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.29

REVEL

Uncertain

0.41

Sift

Uncertain

0.0060

Sift4G

Benign

0.14

Polyphen

0.99

Vest4

0.63

MVP

0.63

MPC

0.72

ClinPred

0.086

GERP RS

6.1

Varity_R

0.13

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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