Genetic Variant NM_001002010.5:c.-197C>T (chr7-33062902-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001002010.5(NT5C3A):c.-197C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 969,208 control chromosomes in the GnomAD database, including 242,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 40222 hom., cov: 33)

Exomes 𝑓: 0.70 ( 202517 hom. )

Consequence

NT5C3A
NM_001002010.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.438

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-33062902-G-A is Benign according to our data. Variant chr7-33062902-G-A is described in ClinVar as [Benign]. Clinvar id is 1295988.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5 link	c.-197C>T		upstream_gene_variant		ENST00000610140.7	NP_001002010.2	Q9H0P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7 link	c.-197C>T		upstream_gene_variant		1	NM_001002010.5	ENSP00000476480.2		X6RM59
NT5C3A	ENST00000456458.5 link	n.-182C>T		upstream_gene_variant		1		ENSP00000389676.2		F8WDR0

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110115

AN:

151860

Hom.:

40175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.788

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.618

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.696

GnomAD4 exome

AF:

0.702

AC:

573380

AN:

817230

Hom.:

202517

AF XY:

0.698

AC XY:

293330

AN XY:

420454

show subpopulations

Gnomad4 AFR exome

AF:

0.805

Gnomad4 AMR exome

AF:

0.799

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.648

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.758

Gnomad4 NFE exome

AF:

0.705

Gnomad4 OTH exome

AF:

0.686

GnomAD4 genome

AF:

0.725

AC:

110220

AN:

151978

Hom.:

40222

Cov.:

AF XY:

0.727

AC XY:

53975

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.788

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.630

Gnomad4 SAS

AF:

0.623

Gnomad4 FIN

AF:

0.760

Gnomad4 NFE

AF:

0.703

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.653

Hom.:

2147

Bravo

AF:

0.726

Asia WGS

AF:

0.628

AC:

2184

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.87

CADD

Benign

3.5

DANN

Benign

0.89

Splicing

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