X-117945498-T-C

Position:

• chrX-117945498-T-C

Variant summary

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

The NM_001168302.2(KLHL13):​c.128A>G​(p.Gln43Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: KLHL13 NM_001168302.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32

Genes affected

KLHL13 (HGNC:22931): (kelch like family member 13) This gene encodes a BTB and kelch domain containing protein and belongs to the kelch repeat domain containing superfamily of proteins. The encoded protein functions as an adaptor protein that complexes with Cullin 3 and other proteins to form the Cullin 3-based E3 ubiquitin-protein ligase complex. This complex is necessary for proper chromosome segregation and completion of cytokinesis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

KLHL13 (HGNC:):

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/exons	MANE	Protein	UniProt
KLHL13	NM_001168302.2	c.128A>G	p.Gln43Arg	missense_variant	3/8	ENST00000540167.6	NP_001161774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL13	ENST00000540167.6	c.128A>G	p.Gln43Arg	missense_variant	3/8	2	NM_001168302.2	ENSP00000441029.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.185A>G (p.Q62R) alteration is located in exon 3 (coding exon 3) of the KLHL13 gene. This alteration results from a A to G substitution at nucleotide position 185, causing the glutamine (Q) at amino acid position 62 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	.;.;.;T;.;.;.;.;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	.;.;D;D;D;.;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.90	.;.;.;L;.;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.16	N;N;N;N;N;N;N;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.016	D;D;D;D;D;D;D;.;.
Sift4G	Benign	0.35	T;T;T;T;T;T;T;.;.
Polyphen		0.84, 0.080, 0.63	.;.;.;P;.;B;B;P;.
Vest4		0.55
MutPred		0.13		.;.;.;Loss of ubiquitination at K62 (P = 0.0211);.;.;.;.;.;
MVP		0.92
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.35
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-117079461;