Genetic Variant KCTD16:p.Pro153Leu (chr5-144207172-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020768.4(KCTD16):c.458C>T(p.Pro153Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,612,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P153T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

KCTD16
NM_020768.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13864794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020768.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD16	NM_020768.4	MANE Select	c.458C>T	p.Pro153Leu	missense	Exon 3 of 4	NP_065819.1	Q68DU8
KCTD16	NM_001370486.1		c.458C>T	p.Pro153Leu	missense	Exon 2 of 3	NP_001357415.1	Q68DU8
KCTD16	NM_001370487.1		c.458C>T	p.Pro153Leu	missense	Exon 2 of 3	NP_001357416.1	Q68DU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD16	ENST00000512467.6	TSL:1 MANE Select	c.458C>T	p.Pro153Leu	missense	Exon 3 of 4	ENSP00000424151.1	Q68DU8
	KCTD16	ENST00000507359.3	TSL:1	c.458C>T	p.Pro153Leu	missense	Exon 2 of 3	ENSP00000426548.1	Q68DU8

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.00144

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250310

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000103

AC:

AN:

1460676

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.000135

AC:

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111492

Other (OTH)

AF:

0.0000995

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00111

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00144

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000314

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.018

Eigen

Benign

-0.027

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

4.9

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.90

REVEL

Benign

0.068

Sift

Benign

0.053

Sift4G

Benign

0.48

Polyphen

0.36

Vest4

0.47

MutPred

0.39

Loss of disorder (P = 0.0296)

MVP

0.13

MPC

0.31

ClinPred

0.18

GERP RS

5.1

Varity_R

0.13

gMVP

0.72

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over