Variant 16-67293567-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001100915.3(KCTD19):c.2195G>A(p.Ser732Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,102 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 3 hom. )

Consequence

KCTD19
NM_001100915.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.257

Variant links:

Genes affected

KCTD19 (HGNC:24753): (potassium channel tetramerization domain containing 19) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

KCTD19 links:

KCTD19 (HGNC:):

KCTD19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003976971).

BP6

Variant 16-67293567-C-T is Benign according to our data. Variant chr16-67293567-C-T is described in ClinVar as [Benign]. Clinvar id is 770633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000668 (977/1461840) while in subpopulation AFR AF= 0.0163 (545/33478). AF 95% confidence interval is 0.0151. There are 3 homozygotes in gnomad4_exome. There are 448 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD19	NM_001100915.3 linkuse as main transcript	c.2195G>A	p.Ser732Asn	missense_variant	12/16	ENST00000304372.6	NP_001094385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD19	ENST00000304372.6 linkuse as main transcript	c.2195G>A	p.Ser732Asn	missense_variant	12/16	1	NM_001100915.3	ENSP00000305702.5		Q17RG1

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

694

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00135

AC:

338

AN:

249482

Hom.:

AF XY:

0.000983

AC XY:

133

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000668

AC:

977

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000616

AC XY:

448

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.00455

AC:

693

AN:

152262

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.00532

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00153

AC:

185

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0026

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.15

.;N

REVEL

Benign

0.16

Sift

Uncertain

0.0040

.;D

Sift4G

Benign

0.075

T;T

Polyphen

0.0

.;B

Vest4

0.13

MVP

0.56

MPC

0.26

ClinPred

0.020

GERP RS

1.4

Varity_R

0.085

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