rs1050288

Positions:

• chr12-27802363-C-T

Variant summary

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

The NM_020782.2(KLHL42):​c.*4197C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,058 control chromosomes in the GnomAD database, including 10,395 homozygotes. 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 0.36 (10395 hom., cov: 32)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: KLHL42 NM_020782.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

Genes affected

KLHL42 (HGNC:29252): (kelch like family member 42) Contributes to ubiquitin-protein transferase activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process; protein polyubiquitination; and regulation of microtubule-based process. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL42	NM_020782.2	c.*4197C>T		3_prime_UTR_variant	3/3	ENST00000381271.7	NP_065833.1
KLHL42	XM_017019698.3	c.*5073C>T		3_prime_UTR_variant	3/3		XP_016875187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL42	ENST00000381271.7	c.*4197C>T		3_prime_UTR_variant	3/3	1	NM_020782.2	ENSP00000370671	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54822 AN: 151924 Hom.: 10376 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 FIN exome AF: 0.214

GnomAD4 genome AF: 0.361 AC: 54871 AN: 152044 Hom.: 10395 Cov.: 32 AF XY: 0.369 AC XY: 27410 AN XY: 74316

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.401

Alfa AF: 0.359 Hom.: 4109

Bravo AF: 0.377

Asia WGS AF: 0.518 AC: 1799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1050288; hg19: chr12-27955296; COSMIC: COSV100792374; COSMIC: COSV100792374;