Variant chr16-29925829-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_178863.5(KCTD13):c.205A>C(p.Met69Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KCTD13
NM_178863.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

Variant links:

Genes affected

KCTD13 (HGNC:22234): (potassium channel tetramerization domain containing 13) Enables identical protein binding activity and small GTPase binding activity. Contributes to ubiquitin-protein transferase activity. Involved in several processes, including cellular protein metabolic process; negative regulation of Rho protein signal transduction; and stress fiber assembly. Located in nuclear body. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

KCTD13 links:

KCTD13 (HGNC:):

KCTD13 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24653518).

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD13	NM_178863.5 linkuse as main transcript	c.205A>C	p.Met69Leu	missense_variant	1/6	ENST00000568000.6	NP_849194.1	Q8WZ19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD13	ENST00000568000.6 linkuse as main transcript	c.205A>C	p.Met69Leu	missense_variant	1/6	1	NM_178863.5	ENSP00000455785.1		Q8WZ19

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250308

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.0000579

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:

0.0000116

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000671

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:

0.0000166

GnomAD4 genome

AF:

0.000145

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000530

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

Jan 24, 2024

The c.205A>C (p.M69L) alteration is located in exon 1 (coding exon 1) of the KCTD13 gene. This alteration results from a A to C substitution at nucleotide position 205, causing the methionine (M) at amino acid position 69 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Uncertain

0.61

D;D;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.065

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.8

D;.;.

Sift

Benign

0.040

D;.;.

Sift4G

Uncertain

0.049

D;T;.

Polyphen

0.60

P;.;.

Vest4

0.50

MutPred

0.70

Loss of ubiquitination at K67 (P = 0.1062);Loss of ubiquitination at K67 (P = 0.1062);Loss of ubiquitination at K67 (P = 0.1062);

MVP

0.80

MPC

1.1

ClinPred

0.17

GERP RS

5.1

Varity_R

0.69

gMVP

0.85

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