NM_198353.3:c.962-13127A>C

Variant names:

• chr4-44188377-T-G
• rs716890
• NM_198353.3:c.962-13127A>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.962-13127A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,146 control chromosomes in the GnomAD database, including 1,912 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 0.15 (1912 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 6 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD8	NM_198353.3	c.962-13127A>C		intron_variant	Intron 1 of 1	ENST00000360029.4	NP_938167.1
KCTD8	XM_011513690.4	c.1046-13127A>C		intron_variant	Intron 2 of 2		XP_011511992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD8	ENST00000360029.4	c.962-13127A>C		intron_variant	Intron 1 of 1	1	NM_198353.3	ENSP00000353129.3
KCTD8	ENST00000515268.1	c.167-13127A>C		intron_variant	Intron 3 of 3	3		ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23299 AN: 152026 Hom.: 1911 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.153 AC: 23306 AN: 152146 Hom.: 1912 Cov.: 32 AF XY: 0.156 AC XY: 11586 AN XY: 74394

African (AFR) AF: 0.157 AC: 6524 AN: 41526

American (AMR) AF: 0.117 AC: 1783 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1318 AN: 5158

South Asian (SAS) AF: 0.140 AC: 676 AN: 4816

European-Finnish (FIN) AF: 0.200 AC: 2114 AN: 10576

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

European-Non Finnish (NFE) AF: 0.150 AC: 10230 AN: 67986

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.149 Hom.: 927

Bravo AF: 0.149

Asia WGS AF: 0.226 AC: 785 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	2.2
DANN	Benign	0.44
PhyloP100		-0.28
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: rs716890; hg19: chr4-44190394;