rs11191553

chr10-103091639-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001351169.2(NT5C2):c.1160-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,597,430 control chromosomes in the GnomAD database, including 75,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7526 hom., cov: 33)
  • Exomes 𝑓: 0.30 (67925 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.557

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 10-103091639-G-T is Benign according to our data. Variant chr10-103091639-G-T is described in ClinVar as [Benign]. Clinvar id is 667744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C2	NM_001351169.2	c.1160-24C>A		intron_variant		ENST00000404739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C2	ENST00000404739.8	c.1160-24C>A		intron_variant		1	NM_001351169.2	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47383 AN: 151966 Hom.: 7520 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.286 AC: 71529 AN: 250322 Hom.: 10616 AF XY: 0.287 AC XY: 38864 AN XY: 135324

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.302 AC: 436583 AN: 1445346 Hom.: 67925 Cov.: 27 AF XY: 0.301 AC XY: 216570 AN XY: 719950

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.312 AC: 47414 AN: 152084 Hom.: 7526 Cov.: 33 AF XY: 0.307 AC XY: 22857 AN XY: 74360

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.362

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: 0.320 Hom.: 7861

Bravo AF: 0.310

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.66
Cadd	Benign	15
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11191553; hg19: chr10-104851396; COSMIC: COSV58414866; COSMIC: COSV58414866;