4-44356395-A-G

Position:

• chr4-44356395-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD8	NM_198353.3	c.961+91168T>C		intron_variant		ENST00000360029.4	NP_938167.1
KCTD8	XM_011513690.4	c.962-62908T>C		intron_variant			XP_011511992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD8	ENST00000360029.4	c.961+91168T>C		intron_variant		1	NM_198353.3	ENSP00000353129.3
KCTD8	ENST00000515268.1	c.50-62564T>C		intron_variant		3		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

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.0914

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.131

Alfa AF: 0.151 Hom.: 3737

Bravo AF: 0.117

Asia WGS AF: 0.204 AC: 710 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	1.6
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs6447330; hg19: chr4-44358412;