Variant 11-78023182-G-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_023930.4(KCTD14):c.68C>A(p.Ser23Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,599,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.000083 ( 0 hom. )

Consequence

KCTD14
NM_023930.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.173

Variant links:

Genes affected

KCTD14 (HGNC:23295): (potassium channel tetramerization domain containing 14) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

KCTD14 links:

NDUFC2-KCTD14 (HGNC:):

NDUFC2-KCTD14 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=0.016370475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCTD14	NM_023930.4 linkuse as main transcript	c.68C>A	p.Ser23Tyr	missense_variant	1/2	ENST00000353172.6
NDUFC2-KCTD14	NM_001203262.2 linkuse as main transcript	c.*1-5912C>A		intron_variant
LOC124902723	XR_007062795.1 linkuse as main transcript	n.479+161G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD14	ENST00000353172.6 linkuse as main transcript	c.68C>A	p.Ser23Tyr	missense_variant	1/2	1	NM_023930.4	P1	Q9BQ13-1
KCTD14	ENST00000533144.1 linkuse as main transcript	c.1-5912C>A		intron_variant		1			Q9BQ13-2
	ENST00000526730.1 linkuse as main transcript	n.89+161G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

229670

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

126234

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000868

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000829

AC:

120

AN:

1447342

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

720290

show subpopulations

Gnomad4 AFR exome

AF:

0.000984

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000932

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000677

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.000447

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000925

Hom.:

Bravo

AF:

0.000431

ExAC

AF:

0.000166

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 09, 2021

The c.68C>A (p.S23Y) alteration is located in exon 1 (coding exon 1) of the KCTD14 gene. This alteration results from a C to A substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a tyrosine (Y). 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

0.091

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.1

DANN

Benign

0.76

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.42

M_CAP

Benign

0.037

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.10

REVEL

Benign

0.079

Sift

Benign

0.17

Sift4G

Uncertain

0.0080

Polyphen

0.98

Vest4

0.20

MVP

0.77

MPC

0.34

ClinPred

0.024

GERP RS

-0.27

Varity_R

0.062

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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