Variant 3-183650428-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000242810.11(KLHL24):c.72A>T(p.Arg24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,614 control chromosomes in the GnomAD database, including 64,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9387 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55368 hom. )

Consequence

KLHL24
ENST00000242810.11 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.280

Variant links:

Genes affected

KLHL24 (HGNC:25947): (kelch like family member 24) The protein encoded by this gene is a ubiquitin ligase substrate receptor and is regulated by autoubiquitination. Variations in the translation initiation codon of this gene have been found, which result in an N-terminally truncated but more stable protein due to loss of the autoubiquitination function. The more stable mutant protein causes an increased ubiquitin and degradation of keratin 14, which leads to skin fragility and the potentially life-threatening disease epidermolysis bullosa. The encoded protein is also involved in the regulation of kainate receptors. [provided by RefSeq, Mar 2017]

KLHL24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-183650428-A-T is Benign according to our data. Variant chr3-183650428-A-T is described in ClinVar as [Benign]. Clinvar id is 1302789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL24	NM_017644.3 linkuse as main transcript	c.72A>T	p.Arg24=	synonymous_variant	3/8	ENST00000242810.11	NP_060114.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL24	ENST00000242810.11 linkuse as main transcript	c.72A>T	p.Arg24=	synonymous_variant	3/8	1	NM_017644.3	ENSP00000242810	P1	Q6TFL4-1

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50856

AN:

151918

Hom.:

9366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.346

GnomAD3 exomes

AF:

0.286

AC:

71870

AN:

251086

Hom.:

11340

AF XY:

0.276

AC XY:

37554

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.495

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.473

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.269

AC:

393324

AN:

1461576

Hom.:

55368

Cov.:

AF XY:

0.266

AC XY:

193075

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.504

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.468

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.335

AC:

50923

AN:

152038

Hom.:

9387

Cov.:

AF XY:

0.329

AC XY:

24486

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.476

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.281

Hom.:

2114

Bravo

AF:

0.356

Asia WGS

AF:

0.326

AC:

1134

AN:

3478

EpiCase

AF:

0.273

EpiControl

AF:

0.276

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.1

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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