Variant 5-144473992-C-T 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_020768.4(KCTD16):c.1165C>T(p.Leu389Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

KCTD16
NM_020768.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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:

Genome browser will be placed here

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=0.005680263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD16	NM_020768.4 linkuse as main transcript	c.1165C>T	p.Leu389Phe	missense_variant	4/4	ENST00000512467.6	NP_065819.1	Q68DU8A8K8W2
KCTD16	NM_001370486.1 linkuse as main transcript	c.1165C>T	p.Leu389Phe	missense_variant	3/3		NP_001357415.1
KCTD16	NM_001370487.1 linkuse as main transcript	c.1165C>T	p.Leu389Phe	missense_variant	3/3		NP_001357416.1
KCTD16	XM_005268493.3 linkuse as main transcript	c.1165C>T	p.Leu389Phe	missense_variant	3/3		XP_005268550.1	Q68DU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD16	ENST00000512467.6 linkuse as main transcript	c.1165C>T	p.Leu389Phe	missense_variant	4/4	1	NM_020768.4	ENSP00000424151.1		Q68DU8
KCTD16	ENST00000507359.3 linkuse as main transcript	c.1165C>T	p.Leu389Phe	missense_variant	3/3	1		ENSP00000426548.1		Q68DU8

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0000655

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:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

250238

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.0000636

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:

0.0000462

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000183

AC:

267

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

149

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:

0.000150

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000447

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000411

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

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 07, 2023

The c.1165C>T (p.L389F) alteration is located in exon 4 (coding exon 2) of the KCTD16 gene. This alteration results from a C to T substitution at nucleotide position 1165, causing the leucine (L) at amino acid position 389 to be replaced by a phenylalanine (F). 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

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.0099

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.51

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.96

D;D

Vest4

0.32

MVP

0.18

MPC

0.45

ClinPred

0.059

GERP RS

4.4

Varity_R

0.14

gMVP

0.21

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