ENST00000674696.1:c.-24-34839T>C

Variant names:

• chr10-103209821-A-G
• rs11191612
• ENST00000674696.1:c.-24-34839T>C

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-24-34839T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,998 control chromosomes in the GnomAD database, including 9,893 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 0.36 (9893 hom., cov: 31)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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):

• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 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.-24-34839T>C		intron_variant	Intron 1 of 17			ENSP00000502679.1
NT5C2	ENST00000675326.1	c.-168-28493T>C		intron_variant	Intron 1 of 18			ENSP00000502205.1
NT5C2	ENST00000676428.1	c.-117-11964T>C		intron_variant	Intron 1 of 18			ENSP00000501689.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54384 AN: 151882 Hom.: 9889 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.358 AC: 54415 AN: 151998 Hom.: 9893 Cov.: 31 AF XY: 0.354 AC XY: 26274 AN XY: 74294

African (AFR) AF: 0.405 AC: 16793 AN: 41418

American (AMR) AF: 0.312 AC: 4762 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5172

South Asian (SAS) AF: 0.261 AC: 1260 AN: 4822

European-Finnish (FIN) AF: 0.290 AC: 3071 AN: 10574

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24492 AN: 67966

Other (OTH) AF: 0.351 AC: 739 AN: 2108

Alfa AF: 0.358 Hom.: 2705

Bravo AF: 0.363

Asia WGS AF: 0.281 AC: 979 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	0.49
DANN	Benign	0.38
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs11191612; hg19: chr10-104969578;