rs34758128

Positions:

• chr10-103090863-A-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.1272+73T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,594,456 control chromosomes in the GnomAD database, including 6,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (504 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6289 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.609

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=-0.85).
• BP6: Variant 10-103090863-A-C is Benign according to our data. Variant chr10-103090863-A-C is described in ClinVar as [Benign]. Clinvar id is 1237292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.1272+73T>G		intron_variant		ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.1272+73T>G		intron_variant		1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10557 AN: 151628 Hom.: 504 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0874 AC: 126044 AN: 1442710 Hom.: 6289 Cov.: 26 AF XY: 0.0859 AC XY: 61706 AN XY: 718692

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.0437

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0212

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0992

Gnomad4 OTH exome AF: 0.0771

GnomAD4 genome AF: 0.0695 AC: 10551 AN: 151746 Hom.: 504 Cov.: 32 AF XY: 0.0683 AC XY: 5066 AN XY: 74170

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0541

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0231

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0915 Hom.: 123

Bravo AF: 0.0636

Asia WGS AF: 0.0120 AC: 41 AN: 3474

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	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.42

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: rs34758128; hg19: chr10-104850620;