rs2465941

Variant names:

• chrX-118003968-G-A
• rs2465941
• NM_001168302.2:c.50+24456C>T

Variant summary

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

The NM_001168302.2(KLHL13):​c.50+24456C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 110,855 control chromosomes in the GnomAD database, including 127 homozygotes. There are 813 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 0.028 (127 hom., 813 hem., cov: 22)
• Consequence: KLHL13 NM_001168302.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL13	NM_001168302.2	c.50+24456C>T		intron_variant	Intron 2 of 7	ENST00000540167.6	NP_001161774.1
KLHL13	NM_001168301.2	c.50+24456C>T		intron_variant	Intron 2 of 7		NP_001161773.1
KLHL13	NM_001394866.1	c.-28-58393C>T		intron_variant	Intron 1 of 6		NP_001381795.1
KLHL13	NM_001168303.4	c.-55-58393C>T		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.50+24456C>T		intron_variant	Intron 2 of 7	2	NM_001168302.2	ENSP00000441029.1
KLHL13	ENST00000371882.5	c.-28-58393C>T		intron_variant	Intron 1 of 6	1		ENSP00000360949.2
KLHL13	ENST00000541812.5	c.50+24456C>T		intron_variant	Intron 2 of 7	2		ENSP00000444450.1
KLHL13	ENST00000453826.1	c.51-20423C>T		intron_variant	Intron 1 of 3	5		ENSP00000393807.2

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 3126 AN: 110806 Hom.: 126 Cov.: 22 AF XY: 0.0246 AC XY: 812 AN XY: 33032

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000386

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00840

Gnomad NFE AF: 0.000283

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0282 AC: 3131 AN: 110855 Hom.: 127 Cov.: 22 AF XY: 0.0246 AC XY: 813 AN XY: 33091

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.000379

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000387

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000283

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00595 Hom.: 186

Bravo AF: 0.0341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2465941; hg19: chrX-117137931;