rs12261294

Variant names:

• chr10-103175195-C-T
• rs12261294
• NM_001351169.2:c.-24-213G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001351169.2(NT5C2):​c.-24-213G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,860 control chromosomes in the GnomAD database, including 1,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1781 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.270
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-103175195-C-T is Benign according to our data. Variant chr10-103175195-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237245.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.-24-213G>A		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.-24-213G>A		intron_variant	Intron 2 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22790 AN: 151742 Hom.: 1778 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.150 AC: 22812 AN: 151860 Hom.: 1781 Cov.: 32 AF XY: 0.148 AC XY: 10985 AN XY: 74208

African (AFR) AF: 0.166 AC: 6852 AN: 41390

American (AMR) AF: 0.154 AC: 2345 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3470

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5176

South Asian (SAS) AF: 0.0837 AC: 403 AN: 4816

European-Finnish (FIN) AF: 0.130 AC: 1363 AN: 10516

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10644 AN: 67936

Other (OTH) AF: 0.152 AC: 319 AN: 2104

Alfa AF: 0.160 Hom.: 260

Bravo AF: 0.153

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.46
PhyloP100		0.27
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: rs12261294; hg19: chr10-104934952;