Variant 16-67291319-T-C 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_001100915.3(KCTD19):c.2555A>G(p.Asn852Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KCTD19
NM_001100915.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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:

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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=0.14641425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD19	NM_001100915.3 linkuse as main transcript	c.2555A>G	p.Asn852Ser	missense_variant	14/16	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.2555A>G	p.Asn852Ser	missense_variant	14/16	1	NM_001100915.3	ENSP00000305702.5		Q17RG1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249068

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461084

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 01, 2024

The c.2555A>G (p.N852S) alteration is located in exon 14 (coding exon 14) of the KCTD19 gene. This alteration results from a A to G substitution at nucleotide position 2555, causing the asparagine (N) at amino acid position 852 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0081

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

M_CAP

Benign

0.0083

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.63

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.54

REVEL

Benign

0.067

Sift

Benign

0.13

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.24

MutPred

0.27

Gain of catalytic residue at N852 (P = 0.0998);

MVP

0.71

MPC

0.22

ClinPred

0.18

GERP RS

4.5

Varity_R

0.054

gMVP

0.17

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