10-103261506-G-A

Variant names:

• chr10-103261506-G-A
• rs1163075
• ENST00000674696.1:c.-25+14710C>T

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-25+14710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,004 control chromosomes in the GnomAD database, including 15,107 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 0.44 (15107 hom., cov: 32)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 9 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

ENSG00000306663 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674696.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000674696.1		c.-25+14710C>T		intron	N/A	ENSP00000502679.1
	NT5C2	ENST00000675326.1		c.-169+15648C>T		intron	N/A	ENSP00000502205.1
	NT5C2	ENST00000676428.1		c.-118+15648C>T		intron	N/A	ENSP00000501689.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67573 AN: 151886 Hom.: 15103 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.445 AC: 67605 AN: 152004 Hom.: 15107 Cov.: 32 AF XY: 0.448 AC XY: 33272 AN XY: 74294

African (AFR) AF: 0.437 AC: 18120 AN: 41462

American (AMR) AF: 0.450 AC: 6867 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3466

East Asian (EAS) AF: 0.457 AC: 2363 AN: 5172

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4812

European-Finnish (FIN) AF: 0.475 AC: 5006 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29682 AN: 67960

Other (OTH) AF: 0.435 AC: 917 AN: 2108

Alfa AF: 0.417 Hom.: 8156

Bravo AF: 0.438

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs1163075; hg19: chr10-105021263;