Variant rs142843476 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_152393.4(KLHL40):c.1768_1770del(p.Glu590del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,603,008 control chromosomes in the GnomAD database, including 95 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 39 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 56 hom. )

Consequence

KLHL40
NM_152393.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.88

Variant links:

Genes affected

KLHL40 (HGNC:30372): (kelch like family member 40) This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012]

KLHL40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_152393.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 3-42691888-CGAG-C is Benign according to our data. Variant chr3-42691888-CGAG-C is described in ClinVar as [Benign]. Clinvar id is 262643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL40	NM_152393.4 linkuse as main transcript	c.1768_1770del	p.Glu590del	inframe_deletion	6/6	ENST00000287777.5	NP_689606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL40	ENST00000287777.5 linkuse as main transcript	c.1768_1770del	p.Glu590del	inframe_deletion	6/6	1	NM_152393.4	ENSP00000287777	P1	Q2TBA0-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2346

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00693

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00443

AC:

1109

AN:

250158

Hom.:

AF XY:

0.00319

AC XY:

431

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00166

AC:

2409

AN:

1450786

Hom.:

AF XY:

0.00136

AC XY:

983

AN XY:

722512

show subpopulations

Gnomad4 AFR exome

AF:

0.0542

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.00390

GnomAD4 genome

AF:

0.0154

AC:

2348

AN:

152222

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1119

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.00692

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nemaline myopathy 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over