rs6603364

Positions:

• chrX-118100969-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168302.2(KLHL13):​c.-25+15539A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 110,767 control chromosomes in the GnomAD database, including 1,393 homozygotes. There are 4,140 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1393 hom., 4140 hem., cov: 22)
• Consequence: KLHL13 NM_001168302.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL13	NM_001168302.2	c.-25+15539A>G		intron_variant		ENST00000540167.6
KLHL13	NM_001168301.2	c.-25+16308A>G		intron_variant
KLHL13	NM_001168303.4	c.-56+15539A>G		intron_variant
KLHL13	NM_001394866.1	c.-29+15539A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL13	ENST00000540167.6	c.-25+15539A>G		intron_variant		2	NM_001168302.2
KLHL13	ENST00000371882.5	c.-29+15539A>G		intron_variant		1
KLHL13	ENST00000541812.5	c.-25+16308A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 15518 AN: 110713 Hom.: 1391 Cov.: 22 AF XY: 0.125 AC XY: 4125 AN XY: 32961

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0749

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000844

Gnomad SAS AF: 0.0514

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 15543 AN: 110767 Hom.: 1393 Cov.: 22 AF XY: 0.125 AC XY: 4140 AN XY: 33025

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000846

Gnomad4 SAS AF: 0.0515

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0851 Hom.: 2534

Bravo AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.77
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6603364; hg19: chrX-117234932;