Variant chr13-45194539-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198404.3(KCTD4):c.29A>G(p.Lys10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,612,564 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

KCTD4
NM_198404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

KCTD4 (HGNC:23227): (potassium channel tetramerization domain containing 4) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

KCTD4 links:

GTF2F2 (HGNC:4653): (general transcription factor IIF subunit 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in microtubule cytoskeleton and nucleoplasm. Part of transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2F2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058317512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCTD4	NM_198404.3 linkuse as main transcript	c.29A>G	p.Lys10Arg	missense_variant	2/2	ENST00000379108.2	NP_940686.2
GTF2F2	NM_004128.3 linkuse as main transcript	c.305-12885T>C		intron_variant		ENST00000340473.8	NP_004119.1
GTF2F2	XM_011535052.4 linkuse as main transcript	c.382+11061T>C		intron_variant			XP_011533354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCTD4	ENST00000379108.2 linkuse as main transcript	c.29A>G	p.Lys10Arg	missense_variant	2/2		NM_198404.3	ENSP00000368402	P1
GTF2F2	ENST00000340473.8 linkuse as main transcript	c.305-12885T>C		intron_variant		1	NM_004128.3	ENSP00000340823	P1
GTF2F2	ENST00000706694.1 linkuse as main transcript	c.134-12885T>C		intron_variant, NMD_transcript_variant				ENSP00000516507

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000232

AC:

AN:

249956

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000351

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:

0.000380

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000378

AC:

552

AN:

1460364

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

265

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000293

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:

0.000471

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000217

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000235

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

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

Jun 04, 2024

The c.29A>G (p.K10R) alteration is located in exon 2 (coding exon 1) of the KCTD4 gene. This alteration results from a A to G substitution at nucleotide position 29, causing the lysine (K) at amino acid position 10 to be replaced by an arginine (R). 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

0.076

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

M_CAP

Benign

0.0091

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.16

REVEL

Benign

0.096

Sift

Benign

0.053

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.17

MVP

0.66

ClinPred

0.018

GERP RS

4.3

Varity_R

0.10

gMVP

0.32

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