rs1891293

Variant names:

• chr10-103242040-G-A
• rs1891293
• ENST00000674696.1:c.-25+34176C>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+34176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,798 control chromosomes in the GnomAD database, including 21,407 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 0.53 (21407 hom., cov: 30)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 6 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):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000674696.1		c.-25+34176C>T		intron	N/A	ENSP00000502679.1	P49902-1
	NT5C2	ENST00000675326.1		c.-169+35114C>T		intron	N/A	ENSP00000502205.1	P49902-1
	NT5C2	ENST00000676428.1		c.-118+35114C>T		intron	N/A	ENSP00000501689.1	P49902-1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80206 AN: 151680 Hom.: 21381 Cov.: 30

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.529 AC: 80282 AN: 151798 Hom.: 21407 Cov.: 30 AF XY: 0.526 AC XY: 38979 AN XY: 74156

African (AFR) AF: 0.498 AC: 20604 AN: 41376

American (AMR) AF: 0.536 AC: 8168 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1873 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2787 AN: 5158

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4812

European-Finnish (FIN) AF: 0.523 AC: 5497 AN: 10504

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37710 AN: 67922

Other (OTH) AF: 0.537 AC: 1134 AN: 2110

Alfa AF: 0.542 Hom.: 3910

Bravo AF: 0.535

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		-0.044

Splicing

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

Other links and lift over

dbSNP: rs1891293; hg19: chr10-105001797;