rs1163238

Variant names:

• chr10-103184236-G-A
• rs1163238
• NM_001351169.2:c.-168-2908C>T

Variant summary

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

The NM_001351169.2(NT5C2):​c.-168-2908C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,024 control chromosomes in the GnomAD database, including 13,405 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 0.41 (13405 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.-168-2908C>T		intron_variant	Intron 1 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.-168-2908C>T		intron_variant	Intron 1 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61877 AN: 151906 Hom.: 13393 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.407 AC: 61920 AN: 152024 Hom.: 13405 Cov.: 32 AF XY: 0.400 AC XY: 29715 AN XY: 74298

African (AFR) AF: 0.560 AC: 23230 AN: 41458

American (AMR) AF: 0.342 AC: 5214 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5174

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3047 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25185 AN: 67976

Other (OTH) AF: 0.386 AC: 813 AN: 2106

Alfa AF: 0.385 Hom.: 1492

Bravo AF: 0.417

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.25
PhyloP100		-0.12
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1163238; hg19: chr10-104943993;