rs1128966

Positions:

• chr17-41827597-G-C
• chr17-41827597-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NT5C3B	NM_052935.5	c.597C>G	p.Leu199Leu	synonymous_variant	8/9	ENST00000435506.7	NP_443167.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C3B	ENST00000435506.7	c.597C>G	p.Leu199Leu	synonymous_variant	8/9	5	NM_052935.5	ENSP00000389948.2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104347 AN: 152016 Hom.: 37027 Cov.: 33

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

GnomAD3 exomes AF: 0.758 AC: 190566 AN: 251278 Hom.: 73585 AF XY: 0.763 AC XY: 103626 AN XY: 135830

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 SAS exome AF: 0.805

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.: 0 AF XY: 0.762 AC XY: 287047 AN XY: 376732

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.868

Gnomad4 ASJ exome AF: 0.854

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.686 AC: 104371 AN: 152134 Hom.: 37036 Cov.: 33 AF XY: 0.686 AC XY: 51025 AN XY: 74354

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.721

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	10
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs1128966; hg19: chr17-39983849; COSMIC: COSV54056919; COSMIC: COSV54056919;