Variant rs12262171 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001351169.2(NT5C2):c.407A>G(p.Gln136Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,599,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

NT5C2
NM_001351169.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.62

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:

NT5C2 (HGNC:):

NT5C2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010461003).

BP6

Variant 10-103101309-T-C is Benign according to our data. Variant chr10-103101309-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474946.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000749 (114/152292) while in subpopulation AFR AF= 0.00265 (110/41562). AF 95% confidence interval is 0.00225. There are 0 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C2	NM_001351169.2 linkuse as main transcript	c.407A>G	p.Gln136Arg	missense_variant	7/19	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8 linkuse as main transcript	c.407A>G	p.Gln136Arg	missense_variant	7/19	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000205

AC:

AN:

248608

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134462

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000656

AC:

AN:

1447184

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

720628

show subpopulations

Gnomad4 AFR exome

AF:

0.00253

Gnomad4 AMR exome

AF:

0.0000681

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152292

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.000903

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 45

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.078

T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

.;D;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.31

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.14

MVP

0.39

MPC

0.74

ClinPred

0.021

GERP RS

6.0

Varity_R

0.085

gMVP

0.56

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