rs12413046

Variant names:

• chr10-103111447-A-G
• rs12413046
• NM_001351169.2:c.176-4741T>C

Variant summary

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

The NM_001351169.2(NT5C2):​c.176-4741T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,202 control chromosomes in the GnomAD database, including 840 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 0.089 (840 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 23 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351169.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.176-4741T>C		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.176-4741T>C		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.176-4741T>C		intron	N/A	NP_001338100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.176-4741T>C		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.176-4741T>C		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000674860.1		c.176-4741T>C		intron	N/A	ENSP00000502816.1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13470 AN: 152084 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0886 AC: 13486 AN: 152202 Hom.: 840 Cov.: 32 AF XY: 0.0908 AC XY: 6760 AN XY: 74420

African (AFR) AF: 0.0396 AC: 1643 AN: 41526

American (AMR) AF: 0.136 AC: 2076 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 253 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1436 AN: 5174

South Asian (SAS) AF: 0.184 AC: 887 AN: 4826

European-Finnish (FIN) AF: 0.0744 AC: 788 AN: 10594

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0904 AC: 6147 AN: 68002

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.0761 Hom.: 214

Bravo AF: 0.0915

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.0
DANN	Benign	0.56
PhyloP100		-0.19
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: rs12413046; hg19: chr10-104871204;