17-41835538-C-T

Variant names:

• chr17-41835538-C-T
• rs1319763
• NM_052935.5:c.112-266G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052935.5(NT5C3B):​c.112-266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 688,926 control chromosomes in the GnomAD database, including 204,268 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 0.76 (44428 hom., cov: 30)
  • Exomes 𝑓: 0.77 (159840 hom.)
• Consequence: NT5C3B NM_052935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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]

KLHL10 (HGNC:18829): (kelch like family member 10) The protein encoded by this gene belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain a BACK domain and six C-terminal kelch repeats. Kelch domains are thought to form a four stranded beta-sheet blade structure that can fold into a beta-propeller domain when multiple kelch repeats are found together. Mutations in this gene have been associated with oligozoospermia in some infertile males. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3B	NM_052935.5	c.112-266G>A		intron_variant	Intron 2 of 8	ENST00000435506.7	NP_443167.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3B	ENST00000435506.7	c.112-266G>A		intron_variant	Intron 2 of 8	5	NM_052935.5	ENSP00000389948.2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115741 AN: 151830 Hom.: 44392 Cov.: 30

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.769 AC: 413048 AN: 536978 Hom.: 159840 Cov.: 3 AF XY: 0.772 AC XY: 224523 AN XY: 290868

Gnomad4 AFR exome AF: 0.771

Gnomad4 AMR exome AF: 0.873

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.751

Gnomad4 OTH exome AF: 0.766

GnomAD4 genome AF: 0.762 AC: 115828 AN: 151948 Hom.: 44428 Cov.: 30 AF XY: 0.760 AC XY: 56431 AN XY: 74252

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.770

Alfa AF: 0.771 Hom.: 30944

Bravo AF: 0.780

Asia WGS AF: 0.817 AC: 2843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs1319763; hg19: chr17-39991790;