rs6603364

Variant names:

• chrX-118100969-T-C
• rs6603364
• NM_001168302.2:c.-25+15539A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLHL13	NM_001168302.2	c.-25+15539A>G		intron_variant	Intron 1 of 7	ENST00000540167.6	NP_001161774.1
KLHL13	NM_001168301.2	c.-25+16308A>G		intron_variant	Intron 1 of 7		NP_001161773.1
KLHL13	NM_001394866.1	c.-29+15539A>G		intron_variant	Intron 1 of 6		NP_001381795.1
KLHL13	NM_001168303.4	c.-56+15539A>G		intron_variant	Intron 1 of 6		NP_001161775.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL13	ENST00000540167.6	c.-25+15539A>G		intron_variant	Intron 1 of 7	2	NM_001168302.2	ENSP00000441029.1
KLHL13	ENST00000371882.5	c.-29+15539A>G		intron_variant	Intron 1 of 6	1		ENSP00000360949.2
KLHL13	ENST00000541812.5	c.-25+16308A>G		intron_variant	Intron 1 of 7	2		ENSP00000444450.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 15518 AN: 110713 Hom.: 1391 Cov.: 22

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

African (AFR) AF: 0.326 AC: 9865 AN: 30291

American (AMR) AF: 0.0695 AC: 720 AN: 10360

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 333 AN: 2638

East Asian (EAS) AF: 0.000846 AC: 3 AN: 3545

South Asian (SAS) AF: 0.0515 AC: 137 AN: 2659

European-Finnish (FIN) AF: 0.0501 AC: 297 AN: 5926

Middle Eastern (MID) AF: 0.165 AC: 36 AN: 218

European-Non Finnish (NFE) AF: 0.0736 AC: 3898 AN: 52929

Other (OTH) AF: 0.134 AC: 203 AN: 1520

Alfa AF: 0.112 Hom.: 4946

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
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6603364; hg19: chrX-117234932;