rs1450627002

Variant names:

• chr4-44447740-G-A
• rs1450627002
• NM_198353.3:c.784C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-44447740-G-A
• chr4-44447740-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	NM_198353.3	MANE Select	c.784C>T	p.Pro262Ser	missense	Exon 1 of 2	NP_938167.1	Q6ZWB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	ENST00000360029.4	TSL:1 MANE Select	c.784C>T	p.Pro262Ser	missense	Exon 1 of 2	ENSP00000353129.3	Q6ZWB6
	KCTD8	ENST00000903710.1		c.784C>T	p.Pro262Ser	missense	Exon 1 of 3	ENSP00000573769.1
	KCTD8	ENST00000954398.1		c.784C>T	p.Pro262Ser	missense	Exon 1 of 3	ENSP00000624457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		9.9
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
PromoterAI		-0.0096	Neutral
Varity_R		0.25
gMVP		0.54
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs1450627002; hg19: chr4-44449757;