Variant 1-961629-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000338591.8(KLHL17):c.368A>G(p.Asn123Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00167 in 1,612,742 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

KLHL17
ENST00000338591.8 missense, splice_region

Scores

Splicing: ADA: 0.0007576

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.57

Variant links:

Genes affected

KLHL17 (HGNC:24023): (kelch like family member 17) The protein encoded by this gene is expressed in neurons of most regions of the brain. It contains an N-terminal BTB domain, which mediates dimerization of the protein, and a C-terminal Kelch domain, which mediates binding to F-actin. This protein may play a key role in the regulation of actin-based neuronal function. [provided by RefSeq, Aug 2010]

KLHL17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010320127).

BP6

Variant 1-961629-A-G is Benign according to our data. Variant chr1-961629-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 782832.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL17	NM_198317.3 linkuse as main transcript	c.368A>G	p.Asn123Ser	missense_variant, splice_region_variant	3/12	ENST00000338591.8	NP_938073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL17	ENST00000338591.8 linkuse as main transcript	c.368A>G	p.Asn123Ser	missense_variant, splice_region_variant	3/12	1	NM_198317.3	ENSP00000343930	P1
KLHL17	ENST00000463212.1 linkuse as main transcript	n.181A>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00178

AC:

436

AN:

245612

Hom.:

AF XY:

0.00165

AC XY:

221

AN XY:

133646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00588

Gnomad NFE exome

AF:

0.00170

Gnomad OTH exome

AF:

0.00500

GnomAD4 exome

AF:

0.00171

AC:

2496

AN:

1460426

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1201

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00615

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152316

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000926

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00188

AC:

227

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00160

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.15

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0099

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.025

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.39

REVEL

Benign

0.20

Sift

Benign

0.50

Sift4G

Benign

0.42

Polyphen

0.58

Vest4

0.49

MVP

0.76

ClinPred

0.063

GERP RS

4.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.3

Varity_R

0.12

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00076

dbscSNV1_RF

Benign

0.052

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