chr10-103273258-C-T

Variant names:

• chr10-103273258-C-T
• rs1712517
• ENST00000674696.1:c.-25+2958G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000674696.1(NT5C2):​c.-25+2958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,876 control chromosomes in the GnomAD database, including 21,096 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21096 hom., cov: 31)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 27 publications found

Genes affected

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

NT5C2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000674696.1	c.-25+2958G>A		intron_variant	Intron 1 of 17			ENSP00000502679.1
NT5C2	ENST00000675326.1	c.-169+3896G>A		intron_variant	Intron 1 of 18			ENSP00000502205.1
NT5C2	ENST00000676428.1	c.-118+3896G>A		intron_variant	Intron 1 of 18			ENSP00000501689.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79373 AN: 151758 Hom.: 21073 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 79438 AN: 151876 Hom.: 21096 Cov.: 31 AF XY: 0.526 AC XY: 39071 AN XY: 74222

African (AFR) AF: 0.607 AC: 25144 AN: 41418

American (AMR) AF: 0.493 AC: 7518 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3470

East Asian (EAS) AF: 0.457 AC: 2353 AN: 5150

South Asian (SAS) AF: 0.645 AC: 3106 AN: 4814

European-Finnish (FIN) AF: 0.539 AC: 5685 AN: 10544

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32391 AN: 67910

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.495 Hom.: 37831

Bravo AF: 0.517

Asia WGS AF: 0.546 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.23
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1712517; hg19: chr10-105033015;