NM_001002010.5:c.378T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001002010.5(NT5C3A):c.378T>C(p.Tyr126Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,609,592 control chromosomes in the GnomAD database, including 395,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38911 hom., cov: 32)

Exomes 𝑓: 0.70 ( 356293 hom. )

Consequence

NT5C3A
NM_001002010.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.332

Publications

32 publications found

Variant links:

Genes affected

NT5C3A (HGNC:17820): (5'-nucleotidase, cytosolic IIIA) This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates. The encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and pseudogenes of this gene are located on the long arm of chromosomes 3 and 4. [provided by RefSeq, Mar 2012]

NT5C3A Gene-Disease associations (from GenCC):

hemolytic anemia due to pyrimidine 5' nucleotidase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

NT5C3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 7-33021334-A-G is Benign according to our data. Variant chr7-33021334-A-G is described in ClinVar as Benign. ClinVar VariationId is 440011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.332 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5 link	c.378T>C	p.Tyr126Tyr	synonymous_variant	Exon 5 of 9	ENST00000610140.7	NP_001002010.2	Q9H0P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7 link	c.378T>C	p.Tyr126Tyr	synonymous_variant	Exon 5 of 9	1	NM_001002010.5	ENSP00000476480.2		X6RM59

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108174

AN:

151908

Hom.:

38872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.684

GnomAD2 exomes

AF:

0.683

AC:

171010

AN:

250244

AF XY:

0.676

show subpopulations

Gnomad AFR exome

AF:

0.771

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.754

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.681

GnomAD4 exome

AF:

0.697

AC:

1015392

AN:

1457566

Hom.:

356293

Cov.:

AF XY:

0.693

AC XY:

502456

AN XY:

725208

show subpopulations

African (AFR)

AF:

0.776

AC:

25888

AN:

33358

American (AMR)

AF:

0.768

AC:

34242

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

14484

AN:

26006

East Asian (EAS)

AF:

0.500

AC:

19732

AN:

39462

South Asian (SAS)

AF:

0.611

AC:

52523

AN:

85946

European-Finnish (FIN)

AF:

0.755

AC:

40243

AN:

53318

Middle Eastern (MID)

AF:

0.629

AC:

3613

AN:

5746

European-Non Finnish (NFE)

AF:

0.707

AC:

783995

AN:

1108926

Other (OTH)

AF:

0.676

AC:

40672

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

15687

31374

47062

62749

78436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19718

39436

59154

78872

98590

<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:

0.712

AC:

108269

AN:

152026

Hom.:

38911

Cov.:

AF XY:

0.713

AC XY:

52957

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.770

AC:

31932

AN:

41484

American (AMR)

AF:

0.728

AC:

11125

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1942

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2533

AN:

5176

South Asian (SAS)

AF:

0.605

AC:

2918

AN:

4820

European-Finnish (FIN)

AF:

0.760

AC:

8015

AN:

10550

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.703

AC:

47729

AN:

67936

Other (OTH)

AF:

0.679

AC:

1433

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1579

3158

4736

6315

7894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.709

Hom.:

39585

Bravo

AF:

0.712

Asia WGS

AF:

0.545

AC:

1889

AN:

3460

EpiCase

AF:

0.679

EpiControl

AF:

0.679

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.53

CADD

Benign

0.69

(source)

DANN

Benign

0.80

PhyloP100

-0.33

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

3.0

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

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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