rs12217501

Variant names:

• chr10-103092132-T-C
• rs12217501
• NM_001351169.2:c.1160-517A>G

Variant summary

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

The NM_001351169.2(NT5C2):​c.1160-517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,268 control chromosomes in the GnomAD database, including 827 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 0.088 (827 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 27 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.1160-517A>G		intron_variant	Intron 15 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.1160-517A>G		intron_variant	Intron 15 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13389 AN: 152150 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.0994

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

GnomAD4 genome AF: 0.0880 AC: 13405 AN: 152268 Hom.: 827 Cov.: 32 AF XY: 0.0905 AC XY: 6736 AN XY: 74462

African (AFR) AF: 0.0391 AC: 1626 AN: 41560

American (AMR) AF: 0.135 AC: 2069 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1442 AN: 5178

South Asian (SAS) AF: 0.183 AC: 881 AN: 4820

European-Finnish (FIN) AF: 0.0746 AC: 791 AN: 10604

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6101 AN: 68014

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.0719 Hom.: 149

Bravo AF: 0.0908

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.57
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12217501; hg19: chr10-104851889;