Variant X-23988416-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_030624.3(KLHL15):c.1320C>G(p.Ser440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,210,154 control chromosomes in the GnomAD database, including 11 homozygotes. There are 906 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., 39 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 10 hom. 867 hem. )

Consequence

KLHL15
NM_030624.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.699

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 -15 ACMG points.

BP4

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

BP6

Variant X-23988416-G-C is Benign according to our data. Variant chrX-23988416-G-C is described in ClinVar as [Benign]. Clinvar id is 741691.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.699 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000571 (64/111989) while in subpopulation SAS AF= 0.0237 (63/2662). AF 95% confidence interval is 0.019. There are 1 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 39 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL15	NM_030624.3 linkuse as main transcript	c.1320C>G	p.Ser440=	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.1320C>G	p.Ser440=	synonymous_variant	4/4	2	NM_030624.3	ENSP00000332791	P1

Frequencies

GnomAD3 genomes

AF:

0.000581

AC:

AN:

111936

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

34104

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000658

GnomAD3 exomes

AF:

0.00277

AC:

507

AN:

183130

Hom.:

AF XY:

0.00443

AC XY:

300

AN XY:

67644

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0265

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.00136

AC:

1495

AN:

1098165

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

867

AN XY:

363521

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0262

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000571

AC:

AN:

111989

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

34167

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0237

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000650

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000102

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.4

DANN

Benign

0.67

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