chr10-103179458-T-C

Variant names:

• chr10-103179458-T-C
• rs11191593
• NM_001351169.2:c.-25+1727A>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.-25+1727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 151,878 control chromosomes in the GnomAD database, including 892 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 0.095 (892 hom., cov: 31)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 54 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.-25+1727A>G		intron_variant	Intron 2 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.-25+1727A>G		intron_variant	Intron 2 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14337 AN: 151760 Hom.: 886 Cov.: 31

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0945 AC: 14357 AN: 151878 Hom.: 892 Cov.: 31 AF XY: 0.0965 AC XY: 7160 AN XY: 74232

African (AFR) AF: 0.0602 AC: 2490 AN: 41390

American (AMR) AF: 0.138 AC: 2109 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3464

East Asian (EAS) AF: 0.278 AC: 1432 AN: 5148

South Asian (SAS) AF: 0.184 AC: 884 AN: 4808

European-Finnish (FIN) AF: 0.0741 AC: 782 AN: 10560

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6146 AN: 67936

Other (OTH) AF: 0.106 AC: 223 AN: 2108

Alfa AF: 0.0951 Hom.: 2384

Bravo AF: 0.0981

Asia WGS AF: 0.196 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11191593; hg19: chr10-104939215;