17-41835538-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

KLHL10 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 11

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052935.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3B	NM_052935.5	MANE Select	c.112-266G>A		intron	N/A	NP_443167.4
	NT5C3B	NR_033464.2		n.254-266G>A		intron	N/A
	NT5C3B	NR_033465.2		n.375-266G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3B	ENST00000435506.7	TSL:5 MANE Select	c.112-266G>A		intron	N/A	ENSP00000389948.2	Q969T7-1
	NT5C3B	ENST00000523903.5	TSL:1	n.401-266G>A		intron	N/A
	NT5C3B	ENST00000946251.1		c.112-266G>A		intron	N/A	ENSP00000616310.1

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

African (AFR) AF: 0.771 AC: 11854 AN: 15384

American (AMR) AF: 0.873 AC: 29380 AN: 33664

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 16605 AN: 19520

East Asian (EAS) AF: 0.846 AC: 26421 AN: 31244

South Asian (SAS) AF: 0.800 AC: 49225 AN: 61544

European-Finnish (FIN) AF: 0.657 AC: 20989 AN: 31954

Middle Eastern (MID) AF: 0.786 AC: 3111 AN: 3956

European-Non Finnish (NFE) AF: 0.751 AC: 232572 AN: 309810

Other (OTH) AF: 0.766 AC: 22891 AN: 29902

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

African (AFR) AF: 0.766 AC: 31737 AN: 41414

American (AMR) AF: 0.843 AC: 12855 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2960 AN: 3468

East Asian (EAS) AF: 0.827 AC: 4263 AN: 5152

South Asian (SAS) AF: 0.799 AC: 3849 AN: 4820

European-Finnish (FIN) AF: 0.626 AC: 6597 AN: 10540

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50966 AN: 67994

Other (OTH) AF: 0.770 AC: 1624 AN: 2110

Alfa AF: 0.769 Hom.: 47602

Bravo AF: 0.780

Asia WGS AF: 0.817 AC: 2843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		-0.17
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1319763;

hg19: chr17-39991790;