Variant 17-41838005-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The ENST00000293303.5(KLHL10):c.73G>A(p.Ala25Thr) variant causes a missense 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Consequence

KLHL10
ENST00000293303.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KLHL10. . Gene score misZ 2.7236 (greater than the threshold 3.09). Trascript score misZ 4.4991 (greater than threshold 3.09). GenCC has associacion of gene with male infertility with azoospermia or oligozoospermia due to single gene mutation.

BP4

Computational evidence support a benign effect (MetaRNN=0.10851166).

BP6

Variant 17-41838005-G-A is Benign according to our data. Variant chr17-41838005-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2534219.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLHL10	NM_152467.5 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	1/5	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	3/7		NP_001316524.1
KLHL10	XM_047435897.1 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	2/6		XP_047291853.1
KLHL10	NM_001329596.2 linkuse as main transcript	c.-130G>A		5_prime_UTR_variant	1/5		NP_001316525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KLHL10	ENST00000293303.5 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	1/5	1	NM_152467.5	ENSP00000293303	P1
KLHL10	ENST00000438813.1 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	1/2	4		ENSP00000416221
KLHL10	ENST00000448203.2 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	3/4	4		ENSP00000391983
KLHL10	ENST00000485613.1 linkuse as main transcript	n.181G>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.027

T;T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

.;L;.

MutationTaster

Benign

0.94

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.082

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.18

MutPred

0.44

Gain of glycosylation at A25 (P = 0.0463);Gain of glycosylation at A25 (P = 0.0463);Gain of glycosylation at A25 (P = 0.0463);

MVP

0.30

MPC

0.60

ClinPred

0.20

GERP RS

3.8

Varity_R

0.044

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over