10-103236031-T-C

Variant names:

• chr10-103236031-T-C
• rs4917384
• ENST00000674696.1:c.-25+40185A>G

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-25+40185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,996 control chromosomes in the GnomAD database, including 42,592 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 0.74 (42592 hom., cov: 31)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 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+40185A>G		intron	N/A	ENSP00000502679.1	P49902-1
	NT5C2	ENST00000675326.1		c.-169+41123A>G		intron	N/A	ENSP00000502205.1	P49902-1
	NT5C2	ENST00000676428.1		c.-117-38174A>G		intron	N/A	ENSP00000501689.1	P49902-1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111970 AN: 151878 Hom.: 42530 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.737 AC: 112086 AN: 151996 Hom.: 42592 Cov.: 31 AF XY: 0.729 AC XY: 54173 AN XY: 74288

African (AFR) AF: 0.929 AC: 38575 AN: 41536

American (AMR) AF: 0.710 AC: 10802 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3132 AN: 5152

South Asian (SAS) AF: 0.499 AC: 2401 AN: 4810

European-Finnish (FIN) AF: 0.597 AC: 6289 AN: 10534

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46036 AN: 67958

Other (OTH) AF: 0.724 AC: 1526 AN: 2108

Alfa AF: 0.702 Hom.: 7460

Bravo AF: 0.760

Asia WGS AF: 0.583 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.61
DANN	Benign	0.32
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs4917384; hg19: chr10-104995788;