chrX-118003968-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 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.50+24456C>T		intron	N/A	NP_001161774.1	Q9P2N7-3
	KLHL13	NM_001168301.2		c.50+24456C>T		intron	N/A	NP_001161773.1	Q9P2N7-3
	KLHL13	NM_001394866.1		c.-28-58393C>T		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.50+24456C>T		intron	N/A	ENSP00000441029.1	Q9P2N7-3
	KLHL13	ENST00000371882.5	TSL:1	c.-28-58393C>T		intron	N/A	ENSP00000360949.2	A0A0C4DG80
	KLHL13	ENST00000541812.5	TSL:2	c.50+24456C>T		intron	N/A	ENSP00000444450.1	Q9P2N7-3

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 3126 AN: 110806 Hom.: 126 Cov.: 22

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

African (AFR) AF: 0.0962 AC: 2924 AN: 30409

American (AMR) AF: 0.0154 AC: 160 AN: 10370

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3511

South Asian (SAS) AF: 0.000387 AC: 1 AN: 2585

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5874

Middle Eastern (MID) AF: 0.00922 AC: 2 AN: 217

European-Non Finnish (NFE) AF: 0.000283 AC: 15 AN: 53050

Other (OTH) AF: 0.0185 AC: 28 AN: 1513

Alfa AF: 0.00921 Hom.: 457

Bravo AF: 0.0341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		0.19
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: rs2465941; hg19: chrX-117137931;