4-44447740-G-A

Variant summary

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

The NM_198353.3(KCTD8):c.784C>T(p.Pro262Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD8 NM_198353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.94

Genes affected

KCTD8 (HGNC:22394): (potassium channel tetramerization domain containing 8) Predicted to be involved in regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection; postsynaptic membrane; and presynaptic membrane. Predicted to be integral component of membrane. Predicted to be part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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/exons	MANE	UniProt
KCTD8	NM_198353.3	c.784C>T	p.Pro262Ser	missense_variant	1/2	ENST00000360029.4
KCTD8	XM_011513690.4	c.784C>T	p.Pro262Ser	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD8	ENST00000360029.4	c.784C>T	p.Pro262Ser	missense_variant	1/2	1	NM_198353.3	P1

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

Jul 14, 2023

The c.784C>T (p.P262S) alteration is located in exon 1 (coding exon 1) of the KCTD8 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the proline (P) at amino acid position 262 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
Cadd	Pathogenic	32
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.30
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.39		Loss of sheet (P = 0.0063);
MVP		0.65
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.25
gMVP		0.54

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: chr4-44449757;