Genetic Variant NM_001002010.5:c.894+141G>A (chr7-33015529-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001002010.5(NT5C3A):c.894+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 632,208 control chromosomes in the GnomAD database, including 652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 130 hom., cov: 32)

Exomes 𝑓: 0.030 ( 522 hom. )

Consequence

NT5C3A
NM_001002010.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.215

Publications

0 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

NT5C3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-33015529-C-T is Benign according to our data. Variant chr7-33015529-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229434.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002010.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NT5C3A	NM_001002010.5	MANE Select	c.894+141G>A	intron	N/A	NP_001002010.2	X6RM59
NT5C3A	NM_001374335.1		c.795+141G>A	intron	N/A	NP_001361264.1
NT5C3A	NM_001002009.3		c.792+141G>A	intron	N/A	NP_001002009.1	Q9H0P0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.894+141G>A	intron	N/A	ENSP00000476480.2	X6RM59
NT5C3A	ENST00000456458.5	TSL:1	n.*799+141G>A	intron	N/A	ENSP00000389676.2	F8WDR0
NT5C3A	ENST00000930183.1		c.861+141G>A	intron	N/A	ENSP00000600242.1

Frequencies

GnomAD3 genomes

AF:

0.0328

AC:

4987

AN:

152070

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0540

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.00746

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0353

GnomAD4 exome

AF:

0.0302

AC:

14485

AN:

480020

Hom.:

522

AF XY:

0.0350

AC XY:

8940

AN XY:

255464

show subpopulations

African (AFR)

AF:

0.0530

AC:

684

AN:

12904

American (AMR)

AF:

0.0155

AC:

323

AN:

20890

Ashkenazi Jewish (ASJ)

AF:

0.0403

AC:

577

AN:

14318

East Asian (EAS)

AF:

0.00821

AC:

256

AN:

31200

South Asian (SAS)

AF:

0.121

AC:

5571

AN:

46008

European-Finnish (FIN)

AF:

0.00836

AC:

318

AN:

38028

Middle Eastern (MID)

AF:

0.0519

AC:

105

AN:

2024

European-Non Finnish (NFE)

AF:

0.0199

AC:

5715

AN:

287772

Other (OTH)

AF:

0.0348

AC:

936

AN:

26876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

649

1298

1948

2597

3246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0328

AC:

4989

AN:

152188

Hom.:

130

Cov.:

AF XY:

0.0330

AC XY:

2456

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0538

AC:

2234

AN:

41512

American (AMR)

AF:

0.0238

AC:

364

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.0186

AC:

AN:

5170

South Asian (SAS)

AF:

0.121

AC:

581

AN:

4820

European-Finnish (FIN)

AF:

0.00746

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0203

AC:

1379

AN:

68022

Other (OTH)

AF:

0.0378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

235

470

704

939

1174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0260

Hom.:

Bravo

AF:

0.0322

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.81

PhyloP100

-0.21

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over