Genetic Variant NT5C3A:p.Tyr126Tyr (chr7-33021334-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 440011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-33021334-A-G is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.683

AC:

171010

AN:

250244

Hom.:

59497

AF XY:

0.676

AC XY:

91411

AN XY:

135318

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 SAS exome

AF:

0.608

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

Gnomad4 AFR exome

AF:

0.776

Gnomad4 AMR exome

AF:

0.768

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.755

Gnomad4 NFE exome

AF:

0.707

Gnomad4 OTH exome

AF:

0.676

GnomAD4 genome

AF:

0.712

AC:

108269

AN:

152026

Hom.:

38911

Cov.:

AF XY:

0.713

AC XY:

52957

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.770

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.605

Gnomad4 FIN

AF:

0.760

Gnomad4 NFE

AF:

0.703

Gnomad4 OTH

AF:

0.679

Alfa

AF:

0.701

Hom.:

22804

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

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

DANN

Benign

0.80

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

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