chr8-17561952-G-C

Variant names:

• chr8-17561952-G-C
• rs56335308
• NM_001370338.1:c.1513G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370338.1(SLC7A2):​c.1513G>C​(p.Val505Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC7A2 NM_001370338.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636
• Publications: 13 publications found

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13433972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A2	NM_001370338.1	c.1513G>C	p.Val505Leu	missense_variant	Exon 11 of 13	ENST00000494857.6	NP_001357267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A2	ENST00000494857.6	c.1513G>C	p.Val505Leu	missense_variant	Exon 11 of 13	5	NM_001370338.1	ENSP00000419140.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	5.2
DANN	Benign	0.17
DEOGEN2	Benign	0.098	T;T;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.41	.;T;.;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L;L;.;.;.;.
PhyloP100		0.64
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.80	N;N;N;N;N;.
REVEL	Uncertain	0.37
Sift	Benign	1.0	T;T;T;T;T;.
Sift4G	Benign	0.96	T;T;T;T;T;.
Polyphen		0.0030	B;B;B;B;B;.
Vest4		0.42
MutPred		0.64		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;.;.;
MVP		0.47
MPC		0.021
ClinPred		0.041	T
GERP RS		-3.6
Varity_R		0.029
gMVP		0.41
Mutation Taster		=94/6	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: rs56335308; hg19: chr8-17419461;