Variant rs2303771 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017566.4(KLHDC4):c.305C>T(p.Thr102Ile) variant causes a missense change. The variant allele was found at a frequency of 0.364 in 1,597,314 control chromosomes in the GnomAD database, including 109,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 10758 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98735 hom. )

Consequence

KLHDC4
NM_017566.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.37

Variant links:

Genes affected

KLHDC4 (HGNC:25272): (kelch domain containing 4)

KLHDC4 links:

KLHDC4 (HGNC:):

KLHDC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9858947E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC4	NM_017566.4 linkuse as main transcript	c.305C>T	p.Thr102Ile	missense_variant	4/12	ENST00000270583.10	NP_060036.2	Q8TBB5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC4	ENST00000270583.10 linkuse as main transcript	c.305C>T	p.Thr102Ile	missense_variant	4/12	1	NM_017566.4	ENSP00000270583.4		Q8TBB5-1
KLHDC4	ENST00000567298.5 linkuse as main transcript	n.305C>T		non_coding_transcript_exon_variant	4/17	5		ENSP00000457570.1		Q8TBB5-1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56498

AN:

151824

Hom.:

10751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.392

AC:

98365

AN:

250844

Hom.:

20214

AF XY:

0.394

AC XY:

53461

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.522

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.363

AC:

524358

AN:

1445372

Hom.:

98735

Cov.:

AF XY:

0.368

AC XY:

264715

AN XY:

719744

show subpopulations

Gnomad4 AFR exome

AF:

0.374

Gnomad4 AMR exome

AF:

0.476

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.530

Gnomad4 FIN exome

AF:

0.364

Gnomad4 NFE exome

AF:

0.346

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.372

AC:

56539

AN:

151942

Hom.:

10758

Cov.:

AF XY:

0.377

AC XY:

28006

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.354

Hom.:

21087

Bravo

AF:

0.373

TwinsUK

AF:

0.356

AC:

1319

ALSPAC

AF:

0.354

AC:

1363

ESP6500AA

AF:

0.379

AC:

1665

ESP6500EA

AF:

0.352

AC:

3025

ExAC

AF:

0.392

AC:

47578

Asia WGS

AF:

0.415

AC:

1443

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.8

DANN

Benign

0.069

DEOGEN2

Benign

0.0023

.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.50

T;T;T;T

MetaRNN

Benign

0.00030

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.6

.;N;N;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

3.7

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0010

B;B;B;.

Vest4

0.20

MPC

0.013

ClinPred

0.0079

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.048

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over