Variant 6-97114279-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052904.4(KLHL32):c.1124G>C(p.Ser375Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

KLHL32
NM_052904.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

KLHL32 (HGNC:21221): (kelch like family member 32)

KLHL32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10252315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL32	NM_052904.4 linkuse as main transcript	c.1124G>C	p.Ser375Thr	missense_variant	7/11	ENST00000369261.9	NP_443136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL32	ENST00000369261.9 linkuse as main transcript	c.1124G>C	p.Ser375Thr	missense_variant	7/11	2	NM_052904.4	ENSP00000358265	P1	Q96NJ5-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152174

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251284

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135820

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727238

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.1124G>C (p.S375T) alteration is located in exon 7 (coding exon 6) of the KLHL32 gene. This alteration results from a G to C substitution at nucleotide position 1124, causing the serine (S) at amino acid position 375 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.082

.;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.95

.;.;N

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.39

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.21

MutPred

0.26

.;.;Loss of disorder (P = 0.0808);

MVP

0.46

MPC

0.36

ClinPred

0.12

GERP RS

5.4

Varity_R

0.12

gMVP

0.34

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