rs762443090

Variant names:

• chr3-170467146-C-G
• rs762443090
• NM_020949.3:c.2225G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-170467146-C-G
• chr3-170467146-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020949.3(SLC7A14):​c.2225G>C​(p.Arg742Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R742Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC7A14 NM_020949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30127162).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A14	NM_020949.3	MANE Select	c.2225G>C	p.Arg742Pro	missense	Exon 8 of 8	NP_066000.2	Q8TBB6
	SLC7A14-AS1	NR_135555.1		n.-139C>G		upstream_gene	N/A
	SLC7A14-AS1	NR_135556.1		n.-139C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A14	ENST00000231706.6	TSL:2 MANE Select	c.2225G>C	p.Arg742Pro	missense	Exon 8 of 8	ENSP00000231706.4	Q8TBB6
	ENSG00000285218	ENST00000486975.1	TSL:2	c.391+43819C>G		intron	N/A	ENSP00000417434.1	B4DFI2
	ENSG00000285218	ENST00000471373.5	TSL:4	n.372+6734C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.0080
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.49	N
REVEL	Uncertain	0.44
Sift	Benign	0.055	T
Sift4G	Benign	0.23	T
Polyphen		0.80	P
Vest4		0.43
MutPred		0.26		Loss of MoRF binding (P = 0.0024)
MVP		0.42
MPC		0.24
ClinPred		0.63	D
GERP RS		4.8
Varity_R		0.24
gMVP		0.45
Mutation Taster		=82/18	polymorphism

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: rs762443090; hg19: chr3-170184934;