rs2106683

Positions:

• chrX-118103312-C-T

Variant summary

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

The NM_001168302.2(KLHL13):​c.-25+13196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 110,981 control chromosomes in the GnomAD database, including 1,395 homozygotes. There are 4,242 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 (1395 hom., 4242 hem., cov: 22)
• Consequence: KLHL13 NM_001168302.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL13	NM_001168302.2	c.-25+13196G>A		intron_variant		ENST00000540167.6	NP_001161774.1
KLHL13	NM_001168301.2	c.-25+13965G>A		intron_variant			NP_001161773.1
KLHL13	NM_001168303.4	c.-56+13196G>A		intron_variant			NP_001161775.2
KLHL13	NM_001394866.1	c.-29+13196G>A		intron_variant			NP_001381795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL13	ENST00000540167.6	c.-25+13196G>A		intron_variant		2	NM_001168302.2	ENSP00000441029
KLHL13	ENST00000371882.5	c.-29+13196G>A		intron_variant		1		ENSP00000360949
KLHL13	ENST00000541812.5	c.-25+13965G>A		intron_variant		2		ENSP00000444450

Frequencies

GnomAD3 genomes AF: 0.141 AC: 15619 AN: 110927 Hom.: 1393 Cov.: 22 AF XY: 0.127 AC XY: 4226 AN XY: 33197

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0696

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.000844

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.141 AC: 15645 AN: 110981 Hom.: 1395 Cov.: 22 AF XY: 0.128 AC XY: 4242 AN XY: 33261

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.0702

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.000846

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.134

Alfa AF: 0.117 Hom.: 716

Bravo AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2106683; hg19: chrX-117237275;