GeneBe

NM_052935.5:c.597C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_052935.5(NT5C3B):​c.597C>A​(p.Leu199Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NT5C3B
NM_052935.5 synonymous

Scores

2

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
Synonymous conserved (PhyloP=1.53 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NT5C3BNM_052935.5 linkc.597C>A 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
NT5C3BENST00000435506.7 linkc.597C>A p.Leu199Leu synonymous_variant Exon 8 of 9 5 NM_052935.5 ENSP00000389948.2 Q969T7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251278
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000140
AC:
1
AN:
711934
Hom.:
0
Cov.:
0
AF XY:
0.00000263
AC XY:
1
AN XY:
380816
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
19754
American (AMR)
AF:
0.00
AC:
0
AN:
43874
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21448
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36460
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71494
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53142
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4304
European-Non Finnish (NFE)
AF:
0.00000235
AC:
1
AN:
425726
Other (OTH)
AF:
0.00
AC:
0
AN:
35732
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
9.1
DANN
Benign
0.89
PhyloP100
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Other links and lift over

dbSNP: rs1128966; hg19: chr17-39983849; API