rs2276717
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
The NM_020949.3(SLC7A14):c.988G>A(p.Gly330Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,614,218 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 10 hom. )
Consequence
SLC7A14
NM_020949.3 missense
NM_020949.3 missense
Scores
8
7
3
Clinical Significance
Conservation
PhyloP100: 7.53
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 8: BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when AlphaMissense, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP6
?
Variant 3-170483441-C-T is Benign according to our data. Variant chr3-170483441-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 126446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-170483441-C-T is described in Lovd as [Pathogenic]. Variant chr3-170483441-C-T is described in Lovd as [Likely_benign]. Variant chr3-170483441-C-T is described in Lovd as [Likely_pathogenic].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000827 (126/152326) while in subpopulation EAS AF= 0.0234 (121/5180). AF 95% confidence interval is 0.02. There are 1 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC7A14 | NM_020949.3 | c.988G>A | p.Gly330Arg | missense_variant | 6/8 | ENST00000231706.6 | |
SLC7A14-AS1 | NR_135556.1 | n.215+6568C>T | intron_variant, non_coding_transcript_variant | ||||
SLC7A14-AS1 | NR_135555.1 | n.215+6568C>T | intron_variant, non_coding_transcript_variant | ||||
SLC7A14-AS1 | NR_135557.1 | n.221+6568C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC7A14 | ENST00000231706.6 | c.988G>A | p.Gly330Arg | missense_variant | 6/8 | 2 | NM_020949.3 | P1 | |
SLC7A14-AS1 | ENST00000644993.1 | n.142+6568C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000834 AC: 127AN: 152208Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00173 AC: 434AN: 251458Hom.: 6 AF XY: 0.00157 AC XY: 214AN XY: 135906
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GnomAD4 exome AF: 0.000611 AC: 893AN: 1461892Hom.: 10 Cov.: 31 AF XY: 0.000605 AC XY: 440AN XY: 727246
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GnomAD4 genome ? AF: 0.000827 AC: 126AN: 152326Hom.: 1 Cov.: 32 AF XY: 0.00102 AC XY: 76AN XY: 74474
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Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Pathogenic:2Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Retinitis pigmentosa 68 Pathogenic:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 31, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 27, 2014 | - - |
Pathogenic, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | NM_020949.2:c.988G>A in the SLC7A14 gene has an allele frequency of 0.023 in East Asian subpopulation in the gnomAD database. This c.988G>A (p.Gly330Arg) variant has been observed in multiple individuals affected with autosomal recessive retinitis pigmentosa, including one in homozygous state and two in compound heterozygous state (PMID: 24670872). Experimental studies have shown that G330R expressing cells showed a diffuse pattern of Slc7a14 expression throughout the cytoplasm (PMID: 24670872). Pathogenic computational verdict because pathogenic predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, MutationAssessor, MutationTaster, PrimateAI, REVEL and SIFT. Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PP3, PM3_Strong, PS3, BS1. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Retinal dystrophy Benign:1
Benign, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
SLC7A14-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 17, 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0171);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at