Variant 6-53654329-C-G 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_001003760.5(KLHL31):c.944G>C(p.Cys315Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

KLHL31
NM_001003760.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

KLHL31 (HGNC:21353): (kelch like family member 31) Involved in negative regulation of JNK cascade and negative regulation of protein phosphorylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

KLHL31 links:

LINC01564 (HGNC:51361): (long intergenic non-protein coding RNA 1564)

LINC01564 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=0.07665211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL31	NM_001003760.5 linkuse as main transcript	c.944G>C	p.Cys315Ser	missense_variant	2/3	ENST00000370905.4	NP_001003760.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KLHL31	ENST00000370905.4 linkuse as main transcript	c.944G>C	p.Cys315Ser	missense_variant	2/3	1	NM_001003760.5	ENSP00000359942	P1
KLHL31	ENST00000407079.1 linkuse as main transcript	c.944G>C	p.Cys315Ser	missense_variant	1/2	1		ENSP00000384644	P1
LINC01564	ENST00000701539.1 linkuse as main transcript	n.320-12382C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251442

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Aug 16, 2021

The c.944G>C (p.C315S) alteration is located in exon 2 (coding exon 1) of the KLHL31 gene. This alteration results from a G to C substitution at nucleotide position 944, causing the cysteine (C) at amino acid position 315 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.26

DEOGEN2

Benign

0.0033

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

T;.

M_CAP

Benign

0.0097

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.65

N;N

MutationTaster

Benign

0.91

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

0.94

N;N

REVEL

Benign

0.060

Sift

Benign

0.89

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.41

Gain of disorder (P = 0.005);Gain of disorder (P = 0.005);

MVP

0.63

MPC

0.84

ClinPred

0.061

GERP RS

3.5

Varity_R

0.096

gMVP

0.33

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