Genetic Variant NM_001351169.2:c.1211+20C>A (chr10-103091544-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001351169.2(NT5C2):c.1211+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 1,594,886 control chromosomes in the GnomAD database, including 9,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 881 hom., cov: 33)

Exomes 𝑓: 0.094 ( 8430 hom. )

Consequence

NT5C2
NM_001351169.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.41

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 10-103091544-G-T is Benign according to our data. Variant chr10-103091544-G-T is described in ClinVar as [Benign]. Clinvar id is 380885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2 link	c.1211+20C>A		intron_variant	Intron 16 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8 link	c.1211+20C>A		intron_variant	Intron 16 of 18	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.0940

AC:

14298

AN:

152144

Hom.:

875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0748

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0899

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.127

AC:

31716

AN:

248884

Hom.:

2628

AF XY:

0.127

AC XY:

17100

AN XY:

134556

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.0760

Gnomad EAS exome

AF:

0.274

Gnomad SAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.0783

Gnomad NFE exome

AF:

0.0867

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.0944

AC:

136209

AN:

1442624

Hom.:

8430

Cov.:

AF XY:

0.0973

AC XY:

69948

AN XY:

718868

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.0749

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.0777

Gnomad4 NFE exome

AF:

0.0784

Gnomad4 OTH exome

AF:

0.0992

GnomAD4 genome

AF:

0.0940

AC:

14318

AN:

152262

Hom.:

881

Cov.:

AF XY:

0.0961

AC XY:

7157

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0595

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0700

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.0748

Gnomad4 NFE

AF:

0.0899

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0888

Hom.:

141

Bravo

AF:

0.0977

Asia WGS

AF:

0.196

AC:

678

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 08, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary spastic paraplegia 45

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.74

CADD

Benign

9.5

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over