rs7689563

Variant names:

• chr4-44342924-G-A
• rs7689563
• NM_198353.3:c.961+104639C>T

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+104639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,198 control chromosomes in the GnomAD database, including 1,310 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 (1310 hom., cov: 33)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 2 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 = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD8	NM_198353.3	c.961+104639C>T		intron_variant	Intron 1 of 1	ENST00000360029.4	NP_938167.1
KCTD8	XM_011513690.4	c.962-49437C>T		intron_variant	Intron 1 of 2		XP_011511992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD8	ENST00000360029.4	c.961+104639C>T		intron_variant	Intron 1 of 1	1	NM_198353.3	ENSP00000353129.3
KCTD8	ENST00000515268.1	c.50-49093C>T		intron_variant	Intron 1 of 3	3		ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18237 AN: 152080 Hom.: 1308 Cov.: 33

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.120 AC: 18238 AN: 152198 Hom.: 1310 Cov.: 33 AF XY: 0.122 AC XY: 9044 AN XY: 74386

African (AFR) AF: 0.0487 AC: 2023 AN: 41556

American (AMR) AF: 0.0849 AC: 1298 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 260 AN: 3468

East Asian (EAS) AF: 0.245 AC: 1265 AN: 5160

South Asian (SAS) AF: 0.147 AC: 710 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10570 AN: 68006

Other (OTH) AF: 0.118 AC: 250 AN: 2116

Alfa AF: 0.143 Hom.: 1205

Bravo AF: 0.111

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.53
PhyloP100		0.25
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: rs7689563; hg19: chr4-44344941;