Variant 5-144473717-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.890G>A(p.Gly297Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

KCTD16
NM_020768.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.77

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 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=0.2129696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD16	NM_020768.4 linkuse as main transcript	c.890G>A	p.Gly297Asp	missense_variant	4/4	ENST00000512467.6	NP_065819.1	Q68DU8A8K8W2
KCTD16	NM_001370486.1 linkuse as main transcript	c.890G>A	p.Gly297Asp	missense_variant	3/3		NP_001357415.1
KCTD16	NM_001370487.1 linkuse as main transcript	c.890G>A	p.Gly297Asp	missense_variant	3/3		NP_001357416.1
KCTD16	XM_005268493.3 linkuse as main transcript	c.890G>A	p.Gly297Asp	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.890G>A	p.Gly297Asp	missense_variant	4/4	1	NM_020768.4	ENSP00000424151.1		Q68DU8
KCTD16	ENST00000507359.3 linkuse as main transcript	c.890G>A	p.Gly297Asp	missense_variant	3/3	1		ENSP00000426548.1		Q68DU8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250690

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459362

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000115

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

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Aug 27, 2024

The c.890G>A (p.G297D) 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 890, causing the glycine (G) at amino acid position 297 to be replaced by an aspartic acid (D). 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

0.23

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.013

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.42

N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.63

T;T

Polyphen

0.73

P;P

Vest4

0.48

MutPred

0.14

Loss of methylation at K296 (P = 0.0886);Loss of methylation at K296 (P = 0.0886);

MVP

0.53

MPC

0.72

ClinPred

0.56

GERP RS

6.1

Varity_R

0.13

gMVP

0.39

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