Variant chrX-23988560-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_030624.3(KLHL15):c.1176T>C(p.Thr392=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,210,188 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.00010 ( 0 hom. 42 hem. )

Consequence

KLHL15
NM_030624.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0920

Variant links:

Genes affected

KLHL15 (HGNC:29347): (kelch like family member 15) This gene encodes a member of the kelch-like family of proteins that share a common domain structure consisting of an N-terminal broad-complex, tramtrack, bric-a-brac/poxvirus and zinc finger domain and C-terminal kelch repeat motifs. The encoded protein may be involved in protein ubiquitination and cytoskeletal organization. [provided by RefSeq, Apr 2009]

KLHL15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-23988560-A-G is Benign according to our data. Variant chrX-23988560-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2660176.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-23988560-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.092 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 42 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL15	NM_030624.3 linkuse as main transcript	c.1176T>C	p.Thr392=	synonymous_variant	4/4	ENST00000328046.8	NP_085127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL15	ENST00000328046.8 linkuse as main transcript	c.1176T>C	p.Thr392=	synonymous_variant	4/4	2	NM_030624.3	ENSP00000332791	P1

Frequencies

GnomAD3 genomes

AF:

0.0000714

AC:

AN:

112052

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34204

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

182910

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

67438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000422

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000102

AC:

112

AN:

1098082

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

363438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000277

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000914

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.0000714

AC:

AN:

112106

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34268

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000793

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

KLHL15: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.0

DANN

Benign

0.66

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