dbSNP rs1128966: NT5C3B:p.Leu199Leu (chr17-41827597-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_052935.5(NT5C3B):c.597C>G(p.Leu199Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 855,048 control chromosomes in the GnomAD database, including 241,762 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 0.69 ( 37036 hom., cov: 33)

Exomes 𝑓: 0.76 ( 204726 hom. )

Consequence

NT5C3B
NM_052935.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

Publications

28 publications found

Variant links:

Genes affected

NT5C3B (HGNC:28300): (5'-nucleotidase, cytosolic IIIB) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in exonucleolytic catabolism of deadenylated mRNA. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NT5C3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3B	NM_052935.5 link	c.597C>G	p.Leu199Leu	synonymous_variant	Exon 8 of 9	ENST00000435506.7	NP_443167.4	Q969T7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3B	ENST00000435506.7 link	c.597C>G	p.Leu199Leu	synonymous_variant	Exon 8 of 9	5	NM_052935.5	ENSP00000389948.2		Q969T7-1

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104347

AN:

152016

Hom.:

37027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.827

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.725

GnomAD2 exomes

AF:

0.758

AC:

190566

AN:

251278

AF XY:

0.763

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.874

Gnomad ASJ exome

AF:

0.859

Gnomad EAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.637

Gnomad NFE exome

AF:

0.751

Gnomad OTH exome

AF:

0.778

GnomAD4 exome

AF:

0.757

AC:

532338

AN:

702914

Hom.:

204726

Cov.:

AF XY:

0.762

AC XY:

287047

AN XY:

376732

show subpopulations

African (AFR)

AF:

0.490

AC:

9593

AN:

19568

American (AMR)

AF:

0.868

AC:

38047

AN:

43850

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

18299

AN:

21422

East Asian (EAS)

AF:

0.844

AC:

30724

AN:

36400

South Asian (SAS)

AF:

0.809

AC:

57723

AN:

71350

European-Finnish (FIN)

AF:

0.650

AC:

34505

AN:

53122

Middle Eastern (MID)

AF:

0.782

AC:

3358

AN:

4294

European-Non Finnish (NFE)

AF:

0.752

AC:

313749

AN:

417476

Other (OTH)

AF:

0.743

AC:

26340

AN:

35432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

7033

14065

21098

28130

35163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3000

6000

9000

12000

15000

<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:

0.686

AC:

104371

AN:

152134

Hom.:

37036

Cov.:

AF XY:

0.686

AC XY:

51025

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.497

AC:

20609

AN:

41504

American (AMR)

AF:

0.821

AC:

12548

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2969

AN:

3472

East Asian (EAS)

AF:

0.827

AC:

4272

AN:

5164

South Asian (SAS)

AF:

0.809

AC:

3903

AN:

4826

European-Finnish (FIN)

AF:

0.626

AC:

6613

AN:

10570

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.749

AC:

50961

AN:

67996

Other (OTH)

AF:

0.721

AC:

1525

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1604

3209

4813

6418

8022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.744

Hom.:

13830

Bravo

AF:

0.694

Asia WGS

AF:

0.766

AC:

2663

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

Other links and lift over