Variant chr11-78174115-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001029859.3(KCTD21):c.440A>T(p.Asn147Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KCTD21
NM_001029859.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Variant links:

Genes affected

KCTD21 (HGNC:27452): (potassium channel tetramerization domain containing 21) Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

KCTD21 links:

KCTD21-AS1 (HGNC:48674): (KCTD21 antisense RNA 1)

KCTD21-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28698438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCTD21	NM_001029859.3 linkuse as main transcript	c.440A>T	p.Asn147Ile	missense_variant	2/2	ENST00000340067.4
KCTD21	XM_047426803.1 linkuse as main transcript	c.548A>T	p.Asn183Ile	missense_variant	3/3
KCTD21	XM_006718517.3 linkuse as main transcript	c.440A>T	p.Asn147Ile	missense_variant	3/3
KCTD21	XM_006718518.4 linkuse as main transcript	c.440A>T	p.Asn147Ile	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD21	ENST00000340067.4 linkuse as main transcript	c.440A>T	p.Asn147Ile	missense_variant	2/2	1	NM_001029859.3	P1
KCTD21-AS1	ENST00000662186.1 linkuse as main transcript	n.1123T>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727222

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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 06, 2022

The c.440A>T (p.N147I) alteration is located in exon 2 (coding exon 1) of the KCTD21 gene. This alteration results from a A to T substitution at nucleotide position 440, causing the asparagine (N) at amino acid position 147 to be replaced by an isoleucine (I). 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

0.25

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

0.086

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

D;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.15

T;.

Polyphen

0.41

B;.

Vest4

0.42

MutPred

0.63

Loss of catalytic residue at N147 (P = 0.0058);Loss of catalytic residue at N147 (P = 0.0058);

MVP

0.60

MPC

0.41

ClinPred

0.55

GERP RS

5.8

Varity_R

0.31

gMVP

0.84

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over