Variant 5-144474004-G-A 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_020768.4(KCTD16):c.1177G>A(p.Glu393Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,836 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KCTD16
NM_020768.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

Variant links:

Genes affected

KCTD16 (HGNC:29244): (potassium channel tetramerization domain containing 16) Predicted to be involved in protein homooligomerization. Predicted to act upstream of or within regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection. Predicted to be part of receptor complex. Predicted to be active in postsynaptic membrane and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

KCTD16 links:

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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=0.20938075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCTD16	NM_020768.4 linkuse as main transcript	c.1177G>A	p.Glu393Lys	missense_variant	4/4	ENST00000512467.6
KCTD16	NM_001370486.1 linkuse as main transcript	c.1177G>A	p.Glu393Lys	missense_variant	3/3
KCTD16	NM_001370487.1 linkuse as main transcript	c.1177G>A	p.Glu393Lys	missense_variant	3/3
KCTD16	XM_005268493.3 linkuse as main transcript	c.1177G>A	p.Glu393Lys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD16	ENST00000512467.6 linkuse as main transcript	c.1177G>A	p.Glu393Lys	missense_variant	4/4	1	NM_020768.4	P1
KCTD16	ENST00000507359.3 linkuse as main transcript	c.1177G>A	p.Glu393Lys	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250352

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 03, 2021

The c.1177G>A (p.E393K) alteration is located in exon 4 (coding exon 2) of the KCTD16 gene. This alteration results from a G to A substitution at nucleotide position 1177, causing the glutamic acid (E) at amino acid position 393 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.056

T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.026

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.58

P;P

Vest4

0.56

MutPred

0.23

Gain of methylation at E393 (P = 0.0127);Gain of methylation at E393 (P = 0.0127);

MVP

0.25

MPC

0.36

ClinPred

0.53

GERP RS

6.2

Varity_R

0.60

gMVP

0.55

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