rs10883841

chr10-103174952-T-Cchr10-103174952-T-G

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.7A>G(p.Thr3Ala) variant causes a missense change. The variant allele was found at a frequency of 0.128 in 1,597,198 control chromosomes in the GnomAD database, including 14,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1139 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13470 hom.)
• Consequence: NT5C2 NM_001351169.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.62

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 (MetaRNN=0.0016233623).
• BP6: Variant 10-103174952-T-C is Benign according to our data. Variant chr10-103174952-T-C is described in ClinVar as [Benign]. Clinvar id is 380851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-103174952-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C2	NM_001351169.2	c.7A>G	p.Thr3Ala	missense_variant	3/19	ENST00000404739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C2	ENST00000404739.8	c.7A>G	p.Thr3Ala	missense_variant	3/19	1	NM_001351169.2	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16318 AN: 152084 Hom.: 1138 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.118 AC: 29236 AN: 247866 Hom.: 2013 AF XY: 0.118 AC XY: 15854 AN XY: 133970

Gnomad AFR exome AF: 0.0302

Gnomad AMR exome AF: 0.0805

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.0391

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.130 AC: 187668 AN: 1444996 Hom.: 13470 Cov.: 27 AF XY: 0.128 AC XY: 92065 AN XY: 719810

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0969

Gnomad4 SAS exome AF: 0.0386

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.107 AC: 16314 AN: 152202 Hom.: 1139 Cov.: 32 AF XY: 0.106 AC XY: 7871 AN XY: 74408

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.120

Alfa AF: 0.136 Hom.: 3684

Bravo AF: 0.0993

TwinsUK AF: 0.137 AC: 509

ALSPAC AF: 0.133 AC: 512

ESP6500AA AF: 0.0340 AC: 150

ESP6500EA AF: 0.149 AC: 1282

ExAC AF: 0.114 AC: 13808

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 01, 2016

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. -

Hereditary spastic paraplegia 45 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.
MutationTaster	Benign	0.0012	P;P
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.37	N;N;.
REVEL	Benign	0.075
Sift	Benign	0.055	T;T;.
Sift4G	Uncertain	0.051	T;T;D
Polyphen		0.0040	B;B;.
Vest4		0.17
MPC		0.68
ClinPred		0.015	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.76

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: rs10883841; hg19: chr10-104934709; COSMIC: COSV100583335; COSMIC: COSV100583335;