10-103203294-G-C

Variant names:

• chr10-103203294-G-C
• rs4917999
• ENST00000674696.1:c.-24-28312C>G

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-24-28312C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,298 control chromosomes in the GnomAD database, including 6,387 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 0.29 (6387 hom., cov: 30)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• Publications: 8 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 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.-24-28312C>G		intron	N/A	ENSP00000502679.1	P49902-1
	NT5C2	ENST00000675326.1		c.-168-21966C>G		intron	N/A	ENSP00000502205.1	P49902-1
	NT5C2	ENST00000676428.1		c.-117-5437C>G		intron	N/A	ENSP00000501689.1	P49902-1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43196 AN: 151182 Hom.: 6382 Cov.: 30

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.286 AC: 43230 AN: 151298 Hom.: 6387 Cov.: 30 AF XY: 0.281 AC XY: 20717 AN XY: 73838

African (AFR) AF: 0.297 AC: 12256 AN: 41224

American (AMR) AF: 0.251 AC: 3819 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3468

East Asian (EAS) AF: 0.134 AC: 691 AN: 5152

South Asian (SAS) AF: 0.124 AC: 596 AN: 4816

European-Finnish (FIN) AF: 0.285 AC: 2921 AN: 10266

Middle Eastern (MID) AF: 0.334 AC: 97 AN: 290

European-Non Finnish (NFE) AF: 0.307 AC: 20856 AN: 67892

Other (OTH) AF: 0.287 AC: 602 AN: 2094

Alfa AF: 0.182 Hom.: 395

Bravo AF: 0.285

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		0.89

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4917999;

hg19: chr10-104963051;