Variant 17-41841889-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001329596.2(KLHL10):c.-4C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,613,950 control chromosomes in the GnomAD database, including 473,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44038 hom., cov: 32)

Exomes 𝑓: 0.76 ( 429024 hom. )

Consequence

KLHL10
NM_001329596.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.25

Variant links:

Genes affected

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 links:

KLHL10 (HGNC:):

KLHL10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 17-41841889-C-T is Benign according to our data. Variant chr17-41841889-C-T is described in ClinVar as [Benign]. Clinvar id is 1249063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL10	NM_152467.5 linkuse as main transcript	c.261C>T	p.Pro87Pro	synonymous_variant	2/5	ENST00000293303.5	NP_689680.2	Q6JEL2A0A140VJM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLHL10	ENST00000293303.5 linkuse as main transcript	c.261C>T	p.Pro87Pro	synonymous_variant	2/5	1	NM_152467.5	ENSP00000293303.4	Q6JEL2
KLHL10	ENST00000438813.1 linkuse as main transcript	c.243C>T	p.Pro81Pro	synonymous_variant	2/2	4		ENSP00000416221.1	C9JHB3
KLHL10	ENST00000448203.2 linkuse as main transcript	c.261C>T	p.Pro87Pro	synonymous_variant	4/4	4		ENSP00000391983.2	C9J999
KLHL10	ENST00000485613.1 linkuse as main transcript	n.307C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115318

AN:

151970

Hom.:

44007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.727

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.845

Gnomad ASJ

AF:

0.870

Gnomad EAS

AF:

0.824

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.782

GnomAD3 exomes

AF:

0.783

AC:

195508

AN:

249562

Hom.:

77431

AF XY:

0.784

AC XY:

106185

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.728

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.875

Gnomad EAS exome

AF:

0.820

Gnomad SAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.793

GnomAD4 exome

AF:

0.765

AC:

1117761

AN:

1461862

Hom.:

429024

Cov.:

AF XY:

0.767

AC XY:

557950

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.720

Gnomad4 AMR exome

AF:

0.880

Gnomad4 ASJ exome

AF:

0.870

Gnomad4 EAS exome

AF:

0.839

Gnomad4 SAS exome

AF:

0.828

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.756

Gnomad4 OTH exome

AF:

0.772

GnomAD4 genome

AF:

0.759

AC:

115394

AN:

152088

Hom.:

44038

Cov.:

AF XY:

0.756

AC XY:

56240

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.727

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.870

Gnomad4 EAS

AF:

0.824

Gnomad4 SAS

AF:

0.827

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.762

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.770

Hom.:

22249

Bravo

AF:

0.774

Asia WGS

AF:

0.818

AC:

2846

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spermatogenic failure 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.1

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over