Variant X-87633870-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000373119.9(KLHL4):c.1671A>T(p.Ser557=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,206,816 control chromosomes in the GnomAD database, including 1 homozygotes. There are 140 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 0.00034 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.00030 ( 1 hom. 130 hem. )

Consequence

KLHL4
ENST00000373119.9 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.874

Variant links:

Genes affected

KLHL4 (HGNC:6355): (kelch like family member 4) This gene encodes a member of the kelch family of proteins, which are characterized by kelch repeat motifs and a POZ/BTB protein-binding domain. It is thought that kelch repeats are actin binding domains. However, the specific function of this protein has not been determined. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

KLHL4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-87633870-A-T is Benign according to our data. Variant chrX-87633870-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661012.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.874 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLHL4	NM_019117.5 linkuse as main transcript	c.1671A>T	p.Ser557=	synonymous_variant	8/11	ENST00000373119.9	NP_061990.2
KLHL4	NM_057162.3 linkuse as main transcript	c.1671A>T	p.Ser557=	synonymous_variant	8/11		NP_476503.1
KLHL4	XR_938403.3 linkuse as main transcript	n.1763A>T		non_coding_transcript_exon_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL4	ENST00000373119.9 linkuse as main transcript	c.1671A>T	p.Ser557=	synonymous_variant	8/11	1	NM_019117.5	ENSP00000362211	P1	Q9C0H6-1
KLHL4	ENST00000373114.4 linkuse as main transcript	c.1671A>T	p.Ser557=	synonymous_variant	8/11	1		ENSP00000362206		Q9C0H6-2
KLHL4	ENST00000652270.1 linkuse as main transcript	c.1671A>T	p.Ser557=	synonymous_variant, NMD_transcript_variant	8/12			ENSP00000498718		Q9C0H6-1

Frequencies

GnomAD3 genomes

AF:

0.000341

AC:

AN:

111498

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33666

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.000490

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000363

AC:

AN:

179131

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

63895

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.000415

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000497

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000299

AC:

327

AN:

1095265

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

130

AN XY:

360783

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.000500

GnomAD4 genome

AF:

0.000341

AC:

AN:

111551

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

33729

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000490

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.000431

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

Nov 01, 2022

KLHL4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.4

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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