rs2106683

Variant names:

• chrX-118103312-C-T
• rs2106683
• NM_001168302.2:c.-25+13196G>A

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+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
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168302.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL13	NM_001168302.2	MANE Select	c.-25+13196G>A		intron	N/A	NP_001161774.1	Q9P2N7-3
	KLHL13	NM_001168301.2		c.-25+13965G>A		intron	N/A	NP_001161773.1	Q9P2N7-3
	KLHL13	NM_001394866.1		c.-29+13196G>A		intron	N/A	NP_001381795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL13	ENST00000540167.6	TSL:2 MANE Select	c.-25+13196G>A		intron	N/A	ENSP00000441029.1	Q9P2N7-3
	KLHL13	ENST00000371882.5	TSL:1	c.-29+13196G>A		intron	N/A	ENSP00000360949.2	A0A0C4DG80
	KLHL13	ENST00000541812.5	TSL:2	c.-25+13965G>A		intron	N/A	ENSP00000444450.1	Q9P2N7-3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 15619 AN: 110927 Hom.: 1393 Cov.: 22

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

African (AFR) AF: 0.326 AC: 9932 AN: 30426

American (AMR) AF: 0.0702 AC: 729 AN: 10387

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 335 AN: 2640

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

South Asian (SAS) AF: 0.0498 AC: 132 AN: 2648

European-Finnish (FIN) AF: 0.0492 AC: 293 AN: 5959

Middle Eastern (MID) AF: 0.157 AC: 34 AN: 216

European-Non Finnish (NFE) AF: 0.0743 AC: 3938 AN: 52973

Other (OTH) AF: 0.134 AC: 202 AN: 1512

Alfa AF: 0.117 Hom.: 716

Bravo AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.47
PhyloP100		-1.6
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: rs2106683; hg19: chrX-117237275;