chr10-103243964-T-G

Variant names:

• chr10-103243964-T-G
• rs4917385
• ENST00000674696.1:c.-25+32252A>C

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-25+32252A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,758 control chromosomes in the GnomAD database, including 42,115 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 0.73 (42115 hom., cov: 29)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 14 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000674696.1	c.-25+32252A>C		intron_variant	Intron 1 of 17			ENSP00000502679.1
NT5C2	ENST00000675326.1	c.-169+33190A>C		intron_variant	Intron 1 of 18			ENSP00000502205.1
NT5C2	ENST00000676428.1	c.-118+33190A>C		intron_variant	Intron 1 of 18			ENSP00000501689.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111209 AN: 151640 Hom.: 42054 Cov.: 29

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.734 AC: 111324 AN: 151758 Hom.: 42115 Cov.: 29 AF XY: 0.726 AC XY: 53805 AN XY: 74138

African (AFR) AF: 0.928 AC: 38453 AN: 41436

American (AMR) AF: 0.705 AC: 10721 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2386 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3125 AN: 5150

South Asian (SAS) AF: 0.499 AC: 2396 AN: 4804

European-Finnish (FIN) AF: 0.595 AC: 6237 AN: 10488

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45548 AN: 67898

Other (OTH) AF: 0.722 AC: 1524 AN: 2112

Alfa AF: 0.714 Hom.: 4912

Bravo AF: 0.756

Asia WGS AF: 0.583 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.8
DANN	Benign	0.44
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs4917385; hg19: chr10-105003721;