16-67293709-C-T

Position:

• chr16-67293709-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100915.3(KCTD19):​c.2053G>A​(p.Ala685Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD19 NM_001100915.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.792

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 (HGNC:):

ACMG classification

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=0.057204843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD19	NM_001100915.3	c.2053G>A	p.Ala685Thr	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	c.2053G>A	p.Ala685Thr	missense_variant	12/16	1	NM_001100915.3	ENSP00000305702.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.2053G>A (p.A685T) alteration is located in exon 12 (coding exon 12) of the KCTD19 gene. This alteration results from a G to A substitution at nucleotide position 2053, causing the alanine (A) at amino acid position 685 to be replaced by a threonine (T). 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	0.068
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0051	.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.48	.;N
REVEL	Benign	0.066
Sift	Benign	0.055	.;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0010	.;B
Vest4		0.084
MutPred		0.20		.;Gain of glycosylation at A685 (P = 0.0031);
MVP		0.29
MPC		0.26
ClinPred		0.14	T
GERP RS		-5.0
Varity_R		0.045
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67327612;