rs3963342

Variant names:

• chr4-44298231-C-T
• rs3963342
• NM_198353.3:c.962-122981G>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.962-122981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,008 control chromosomes in the GnomAD database, including 33,918 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 0.67 (33918 hom., cov: 31)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 4 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]

LOC107986275 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	NM_198353.3	MANE Select	c.962-122981G>A		intron	N/A	NP_938167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	ENST00000360029.4	TSL:1 MANE Select	c.962-122981G>A		intron	N/A	ENSP00000353129.3
	KCTD8	ENST00000903710.1		c.962-4744G>A		intron	N/A	ENSP00000573769.1
	KCTD8	ENST00000954398.1		c.1021+25355G>A		intron	N/A	ENSP00000624457.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101420 AN: 151890 Hom.: 33884 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.668 AC: 101509 AN: 152008 Hom.: 33918 Cov.: 31 AF XY: 0.666 AC XY: 49454 AN XY: 74296

African (AFR) AF: 0.670 AC: 27784 AN: 41466

American (AMR) AF: 0.669 AC: 10219 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2293 AN: 3466

East Asian (EAS) AF: 0.705 AC: 3637 AN: 5158

South Asian (SAS) AF: 0.629 AC: 3028 AN: 4814

European-Finnish (FIN) AF: 0.633 AC: 6680 AN: 10558

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45682 AN: 67952

Other (OTH) AF: 0.680 AC: 1434 AN: 2110

Alfa AF: 0.671 Hom.: 106937

Bravo AF: 0.672

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.73
DANN	Benign	0.38
PhyloP100		-0.38
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: rs3963342; hg19: chr4-44300248;