rs10883841

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 12/21 in silico tools predict 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

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.62

Publications

45 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 45
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

NT5C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 380851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2 link	c.7A>G	p.Thr3Ala	missense_variant	Exon 3 of 19	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8 link	c.7A>G	p.Thr3Ala	missense_variant	Exon 3 of 19	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16318

AN:

152084

Hom.:

1138

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.118

AC:

29236

AN:

247866

AF XY:

0.118

show subpopulations

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 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.:

AF XY:

0.128

AC XY:

92065

AN XY:

719810

show subpopulations

African (AFR)

AF:

0.0255

AC:

850

AN:

33302

American (AMR)

AF:

0.0801

AC:

3565

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3896

AN:

25984

East Asian (EAS)

AF:

0.0969

AC:

3834

AN:

39580

South Asian (SAS)

AF:

0.0386

AC:

3310

AN:

85774

European-Finnish (FIN)

AF:

0.155

AC:

8243

AN:

53060

Middle Eastern (MID)

AF:

0.0796

AC:

456

AN:

5728

European-Non Finnish (NFE)

AF:

0.142

AC:

155991

AN:

1097278

Other (OTH)

AF:

0.126

AC:

7523

AN:

59794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

6713

13427

20140

26854

33567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5350

10700

16050

21400

26750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16314

AN:

152202

Hom.:

1139

Cov.:

AF XY:

0.106

AC XY:

7871

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0313

AC:

1301

AN:

41544

American (AMR)

AF:

0.0848

AC:

1297

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

540

AN:

3468

East Asian (EAS)

AF:

0.139

AC:

720

AN:

5184

South Asian (SAS)

AF:

0.0422

AC:

203

AN:

4816

European-Finnish (FIN)

AF:

0.155

AC:

1636

AN:

10586

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10241

AN:

67996

Other (OTH)

AF:

0.120

AC:

253

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

732

1464

2197

2929

3661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

6477

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 01, 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

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.098

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

.;D;D

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

PhyloP100

5.6

PrimateAI

Uncertain

0.60

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

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.76

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over