dbSNP rs11974256: NT5C3A:c.308-114G>A (chr7-33022213-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001002010.5(NT5C3A):c.308-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 671,232 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 91 hom., cov: 33)

Exomes 𝑓: 0.032 ( 637 hom. )

Consequence

NT5C3A
NM_001002010.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.648

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5 link	c.308-114G>A		intron_variant	Intron 3 of 8	ENST00000610140.7	NP_001002010.2	Q9H0P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7 link	c.308-114G>A		intron_variant	Intron 3 of 8	1	NM_001002010.5	ENSP00000476480.2		X6RM59

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4328

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.00744

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0335

GnomAD4 exome

AF:

0.0316

AC:

16414

AN:

518954

Hom.:

637

AF XY:

0.0372

AC XY:

10442

AN XY:

281026

show subpopulations

African (AFR)

AF:

0.0382

AC:

559

AN:

14650

American (AMR)

AF:

0.0142

AC:

432

AN:

30386

Ashkenazi Jewish (ASJ)

AF:

0.0410

AC:

734

AN:

17886

East Asian (EAS)

AF:

0.00817

AC:

256

AN:

31332

South Asian (SAS)

AF:

0.122

AC:

7053

AN:

57646

European-Finnish (FIN)

AF:

0.00845

AC:

282

AN:

33378

Middle Eastern (MID)

AF:

0.0515

AC:

115

AN:

2234

European-Non Finnish (NFE)

AF:

0.0198

AC:

6003

AN:

302886

Other (OTH)

AF:

0.0343

AC:

980

AN:

28556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

741

1482

2224

2965

3706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0284

AC:

4330

AN:

152278

Hom.:

Cov.:

AF XY:

0.0289

AC XY:

2149

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0384

AC:

1595

AN:

41568

American (AMR)

AF:

0.0230

AC:

351

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.0185

AC:

AN:

5184

South Asian (SAS)

AF:

0.120

AC:

581

AN:

4828

European-Finnish (FIN)

AF:

0.00744

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0202

AC:

1376

AN:

68002

Other (OTH)

AF:

0.0360

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

220

439

659

878

1098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0236

Hom.:

Bravo

AF:

0.0274

Asia WGS

AF:

0.0630

AC:

218

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.6

(source)

DANN

Benign

0.48

PhyloP100

0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over