4-44332812-C-T

Variant names:

• chr4-44332812-C-T
• rs17599605
• NM_198353.3:c.961+114751G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198353.3(KCTD8):​c.961+114751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,812 control chromosomes in the GnomAD database, including 2,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2785 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

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.961+114751G>A		intron	N/A	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.961+114751G>A		intron	N/A	ENSP00000353129.3	Q6ZWB6
	KCTD8	ENST00000903710.1		c.962-39325G>A		intron	N/A	ENSP00000573769.1
	KCTD8	ENST00000954398.1		c.962-9167G>A		intron	N/A	ENSP00000624457.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27461 AN: 151694 Hom.: 2781 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.184

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27481 AN: 151812 Hom.: 2785 Cov.: 32 AF XY: 0.188 AC XY: 13934 AN XY: 74188

African (AFR) AF: 0.114 AC: 4734 AN: 41464

American (AMR) AF: 0.232 AC: 3537 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3466

East Asian (EAS) AF: 0.389 AC: 2006 AN: 5162

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4826

European-Finnish (FIN) AF: 0.263 AC: 2773 AN: 10542

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12503 AN: 67808

Other (OTH) AF: 0.186 AC: 391 AN: 2102

Alfa AF: 0.178 Hom.: 3512

Bravo AF: 0.178

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.59
PhyloP100		0.043
Mutation Taster		=100/0	polymorphism (auto)

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: rs17599605; hg19: chr4-44334829;