4-44356395-A-G

Variant names:

• chr4-44356395-A-G
• rs6447330
• NM_198353.3:c.961+91168T>C

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+91168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,234 control chromosomes in the GnomAD database, including 1,356 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 0.12 (1356 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 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.961+91168T>C		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.961+91168T>C		intron	N/A	ENSP00000353129.3
	KCTD8	ENST00000515268.1	TSL:3	c.50-62564T>C		intron	N/A	ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18652 AN: 152116 Hom.: 1354 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.123 AC: 18655 AN: 152234 Hom.: 1356 Cov.: 32 AF XY: 0.122 AC XY: 9098 AN XY: 74422

African (AFR) AF: 0.0514 AC: 2136 AN: 41550

American (AMR) AF: 0.0914 AC: 1398 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1319 AN: 5166

South Asian (SAS) AF: 0.132 AC: 636 AN: 4830

European-Finnish (FIN) AF: 0.138 AC: 1465 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10902 AN: 68010

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.145 Hom.: 5863

Bravo AF: 0.117

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.35
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: rs6447330; hg19: chr4-44358412;