Genetic Variant KCTD12:p.Phe87Leu (chr13-76885888-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138444.4(KCTD12):c.261C>A(p.Phe87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,597,094 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KCTD12
NM_138444.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32

Variant links:

Genes affected

KCTD12 (HGNC:14678): (potassium channel tetramerization domain containing 12) Enables identical protein binding activity. 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]

KCTD12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD12	NM_138444.4 link	c.261C>A	p.Phe87Leu	missense_variant	Exon 1 of 1	ENST00000377474.4	NP_612453.1	Q96CX2A0A140VJM4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD12	ENST00000377474.4 link	c.261C>A	p.Phe87Leu	missense_variant	Exon 1 of 1	6	NM_138444.4	ENSP00000366694.2		Q96CX2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444848

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.43

Sift

Benign

0.038

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.61

MutPred

0.36

Gain of helix (P = 0.0425);

MVP

0.88

MPC

2.0

ClinPred

0.97

GERP RS

3.6

Varity_R

0.52

gMVP

0.58

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over