17-41838005-G-A

Variant names:

• chr17-41838005-G-A
• NM_152467.5:c.73G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_152467.5(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 NM_152467.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.73G>A	p.Ala25Thr	missense_variant	Exon 1 of 5	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.73G>A	p.Ala25Thr	missense_variant	Exon 3 of 7		NP_001316524.1
KLHL10	XM_047435897.1	c.73G>A	p.Ala25Thr	missense_variant	Exon 2 of 6		XP_047291853.1
KLHL10	NM_001329596.2	c.-130G>A		5_prime_UTR_variant	Exon 1 of 5		NP_001316525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.73G>A	p.Ala25Thr	missense_variant	Exon 1 of 5	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.73G>A	p.Ala25Thr	missense_variant	Exon 1 of 2	4		ENSP00000416221.1
KLHL10	ENST00000448203.2	c.73G>A	p.Ala25Thr	missense_variant	Exon 3 of 4	4		ENSP00000391983.2
KLHL10	ENST00000485613.1	n.181G>A		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
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	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	.;L;.
PrimateAI	Benign	0.46	T
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	T
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.

Other links and lift over

hg19: chr17-39994257;