17-41842092-A-G

Variant names:

• chr17-41842092-A-G
• NM_152467.5:c.464A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152467.5(KLHL10):​c.464A>G​(p.Glu155Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLHL10 NM_152467.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.464A>G	p.Glu155Gly	missense_variant	Exon 2 of 5	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.464A>G	p.Glu155Gly	missense_variant	Exon 4 of 7		NP_001316524.1
KLHL10	NM_001329596.2	c.200A>G	p.Glu67Gly	missense_variant	Exon 2 of 5		NP_001316525.1
KLHL10	XM_047435897.1	c.464A>G	p.Glu155Gly	missense_variant	Exon 3 of 6		XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.464A>G	p.Glu155Gly	missense_variant	Exon 2 of 5	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.446A>G	p.Glu149Gly	missense_variant	Exon 2 of 2	4		ENSP00000416221.1
KLHL10	ENST00000485613.1	n.510A>G		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.464A>G (p.E155G) alteration is located in exon 2 (coding exon 2) of the KLHL10 gene. This alteration results from a A to G substitution at nucleotide position 464, causing the glutamic acid (E) at amino acid position 155 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.27
Sift	Benign	0.28	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.028	B;.
Vest4		0.18
MutPred		0.54		Loss of ubiquitination at K159 (P = 0.0653);.;
MVP		0.65
MPC		0.73
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.37
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr17-39998344;