X-117954093-T-C

Variant names:

• chrX-117954093-T-C
• rs2430212
• NM_001168302.2:c.51-8518A>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.51-8518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 110,426 control chromosomes in the GnomAD database, including 10,182 homozygotes. There are 13,845 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 0.44 (10182 hom., 13845 hem., cov: 22)
• Consequence: KLHL13 NM_001168302.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL13	NM_001168302.2	c.51-8518A>G		intron_variant	Intron 2 of 7	ENST00000540167.6	NP_001161774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL13	ENST00000540167.6	c.51-8518A>G		intron_variant	Intron 2 of 7	2	NM_001168302.2	ENSP00000441029.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 48730 AN: 110373 Hom.: 10173 Cov.: 22

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.442 AC: 48805 AN: 110426 Hom.: 10182 Cov.: 22 AF XY: 0.424 AC XY: 13845 AN XY: 32686

African (AFR) AF: 0.832 AC: 25228 AN: 30321

American (AMR) AF: 0.298 AC: 3093 AN: 10384

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 892 AN: 2629

East Asian (EAS) AF: 0.329 AC: 1143 AN: 3471

South Asian (SAS) AF: 0.365 AC: 950 AN: 2602

European-Finnish (FIN) AF: 0.257 AC: 1520 AN: 5913

Middle Eastern (MID) AF: 0.417 AC: 88 AN: 211

European-Non Finnish (NFE) AF: 0.286 AC: 15051 AN: 52702

Other (OTH) AF: 0.438 AC: 664 AN: 1516

Alfa AF: 0.345 Hom.: 47080

Bravo AF: 0.461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2430212; hg19: chrX-117088056;