rs10883830

Positions:

• chr10-103091528-G-A
• chr10-103091528-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001351169.2(NT5C2):​c.1211+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,508,384 control chromosomes in the GnomAD database, including 71,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7541 hom., cov: 32)
  • Exomes 𝑓: 0.30 (63818 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.363

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-103091528-G-A is Benign according to our data. Variant chr10-103091528-G-A is described in ClinVar as [Benign]. Clinvar id is 667762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.1211+36C>T		intron_variant		ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.1211+36C>T		intron_variant		1	NM_001351169.2	ENSP00000383960	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47410 AN: 152008 Hom.: 7535 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.285 AC: 70978 AN: 248614 Hom.: 10521 AF XY: 0.287 AC XY: 38618 AN XY: 134532

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.303 AC: 410742 AN: 1356258 Hom.: 63818 Cov.: 20 AF XY: 0.301 AC XY: 205232 AN XY: 680744

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.312 AC: 47441 AN: 152126 Hom.: 7541 Cov.: 32 AF XY: 0.307 AC XY: 22853 AN XY: 74368

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.314

Alfa AF: 0.327 Hom.: 2178

Bravo AF: 0.310

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs10883830; hg19: chr10-104851285;