rs2276717

Variant names:

• chr3-170483441-C-A
• rs2276717
• NM_020949.3:c.988G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-170483441-C-A
• chr3-170483441-C-G
• chr3-170483441-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020949.3(SLC7A14):​c.988G>T​(p.Gly330Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G330R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC7A14 NM_020949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53
• Publications: 0 publications found

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]

ENSG00000285218 (HGNC:):

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A14	NM_020949.3	c.988G>T	p.Gly330Trp	missense_variant	Exon 6 of 8	ENST00000231706.6	NP_066000.2
SLC7A14-AS1	NR_135555.1	n.215+6568C>A		intron_variant	Intron 2 of 2
SLC7A14-AS1	NR_135556.1	n.215+6568C>A		intron_variant	Intron 2 of 5
SLC7A14-AS1	NR_135557.1	n.221+6568C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A14	ENST00000231706.6	c.988G>T	p.Gly330Trp	missense_variant	Exon 6 of 8	2	NM_020949.3	ENSP00000231706.4
ENSG00000285218	ENST00000486975.1	c.391+60114C>A		intron_variant	Intron 2 of 3	2		ENSP00000417434.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		7.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.76		Loss of ubiquitination at K335 (P = 0.1351);
MVP		0.78
MPC		0.67
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.81
gMVP		0.92
Mutation Taster		=20/80	disease causing

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

Other links and lift over

dbSNP: rs2276717; hg19: chr3-170201230; COSMIC: COSV51590192;