Variant 8-123651747-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001081675.3(KLHL38):c.1180G>C(p.Gly394Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 1,614,128 control chromosomes in the GnomAD database, including 4,573 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.059 ( 441 hom., cov: 34)

Exomes 𝑓: 0.057 ( 4132 hom. )

Consequence

KLHL38
NM_001081675.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

KLHL38 (HGNC:34435): (kelch like family member 38)

KLHL38 links:

ENSG00000253286 (HGNC:):

ENSG00000253286 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025041401).

BP6

Variant 8-123651747-C-G is Benign according to our data. Variant chr8-123651747-C-G is described in ClinVar as [Benign]. Clinvar id is 1245653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL38	NM_001081675.3 linkuse as main transcript	c.1180G>C	p.Gly394Arg	missense_variant	2/4	ENST00000684634.1	NP_001075144.2	Q2WGJ6
KLHL38	XM_047421744.1 linkuse as main transcript	c.1180G>C	p.Gly394Arg	missense_variant	2/4		XP_047277700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLHL38	ENST00000684634.1 linkuse as main transcript	c.1180G>C	p.Gly394Arg	missense_variant	2/4		NM_001081675.3	ENSP00000508228.1	Q2WGJ6
KLHL38	ENST00000325995.7 linkuse as main transcript	c.1180G>C	p.Gly394Arg	missense_variant	1/3	1		ENSP00000321475.7	Q2WGJ6
ENSG00000253286	ENST00000524355.1 linkuse as main transcript	n.245-6502C>G		intron_variant		4
ENSG00000253286	ENST00000652905.1 linkuse as main transcript	n.176-14601C>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9041

AN:

152196

Hom.:

438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0951

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0280

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0651

GnomAD3 exomes

AF:

0.0805

AC:

20065

AN:

249332

Hom.:

1418

AF XY:

0.0834

AC XY:

11286

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.0414

Gnomad AMR exome

AF:

0.0906

Gnomad ASJ exome

AF:

0.0470

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.0302

Gnomad NFE exome

AF:

0.0413

Gnomad OTH exome

AF:

0.0684

GnomAD4 exome

AF:

0.0574

AC:

83928

AN:

1461814

Hom.:

4132

Cov.:

AF XY:

0.0609

AC XY:

44268

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0463

Gnomad4 AMR exome

AF:

0.0886

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.227

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0412

Gnomad4 OTH exome

AF:

0.0722

GnomAD4 genome

AF:

0.0595

AC:

9058

AN:

152314

Hom.:

441

Cov.:

AF XY:

0.0634

AC XY:

4724

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.0950

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.0280

Gnomad4 NFE

AF:

0.0424

Gnomad4 OTH

AF:

0.0687

Alfa

AF:

0.0464

Hom.:

224

Bravo

AF:

0.0597

TwinsUK

AF:

0.0399

AC:

148

ALSPAC

AF:

0.0428

AC:

165

ESP6500AA

AF:

0.0408

AC:

164

ESP6500EA

AF:

0.0443

AC:

370

ExAC

AF:

0.0790

AC:

9559

Asia WGS

AF:

0.199

AC:

691

AN:

3478

EpiCase

AF:

0.0447

EpiControl

AF:

0.0444

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2019	This variant is associated with the following publications: (PMID: 30012220) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.3

REVEL

Benign

0.10

Sift

Benign

0.11

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.043

MutPred

0.20

Gain of solvent accessibility (P = 0.0128);

MPC

0.068

ClinPred

0.0069

GERP RS

3.2

Varity_R

0.13

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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