rs1050288

Variant names:

• chr12-27802363-C-T
• rs1050288
• NM_020782.2:c.*4197C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020782.2. 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
	KLHL42	NM_020782.2	MANE Select	c.*4197C>T		3_prime_UTR	Exon 3 of 3	NP_065833.1	Q9P2K6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL42	ENST00000381271.7	TSL:1 MANE Select	c.*4197C>T		3_prime_UTR	Exon 3 of 3	ENSP00000370671.2	Q9P2K6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.214 AC: 3 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.309 AC: 12811 AN: 41462

American (AMR) AF: 0.490 AC: 7497 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3377 AN: 5164

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4822

European-Finnish (FIN) AF: 0.337 AC: 3558 AN: 10562

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23020 AN: 67952

Other (OTH) AF: 0.401 AC: 848 AN: 2116

Alfa AF: 0.358 Hom.: 6212

Bravo AF: 0.377

Asia WGS AF: 0.518 AC: 1799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		-0.11
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1050288;

hg19: chr12-27955296;

COSMIC: COSV100792374;

COSMIC: COSV100792374;