rs7095304

Variant names:

• chr10-103195038-G-A
• rs7095304
• ENST00000674696.1:c.-24-20056C>T

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-24-20056C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,892 control chromosomes in the GnomAD database, including 7,469 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 0.31 (7469 hom., cov: 32)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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.-24-20056C>T		intron	N/A	ENSP00000502679.1	P49902-1
	NT5C2	ENST00000675326.1		c.-168-13710C>T		intron	N/A	ENSP00000502205.1	P49902-1
	NT5C2	ENST00000676428.1		c.-25+2727C>T		intron	N/A	ENSP00000501689.1	P49902-1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47163 AN: 151774 Hom.: 7463 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.311 AC: 47194 AN: 151892 Hom.: 7469 Cov.: 32 AF XY: 0.306 AC XY: 22742 AN XY: 74218

African (AFR) AF: 0.328 AC: 13588 AN: 41410

American (AMR) AF: 0.263 AC: 4015 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5176

South Asian (SAS) AF: 0.243 AC: 1172 AN: 4820

European-Finnish (FIN) AF: 0.291 AC: 3040 AN: 10458

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 22000 AN: 67972

Other (OTH) AF: 0.311 AC: 657 AN: 2110

Alfa AF: 0.319 Hom.: 9706

Bravo AF: 0.309

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.3
DANN	Benign	0.36
PhyloP100		0.68

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: rs7095304;

hg19: chr10-104954795;