rs1812594

Variant names:

• chr8-25429881-T-C
• rs1812594
• NM_017634.4:c.1146A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-25429881-T-C
• chr8-25429881-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017634.4(KCTD9):​c.1146A>G​(p.Leu382Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,579,304 control chromosomes in the GnomAD database, including 33,022 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 0.18 (2706 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30316 hom.)
• Consequence: KCTD9 NM_017634.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 14 publications found

Genes affected

KCTD9 (HGNC:22401): (potassium channel tetramerization domain containing 9) Enables cullin family protein binding activity; identical protein binding activity; and protein self-association. Predicted to be involved in intracellular signal transduction; protein homooligomerization; and protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.311 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017634.4. 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
	KCTD9	NM_017634.4	MANE Select	c.1146A>G	p.Leu382Leu	synonymous	Exon 12 of 12	NP_060104.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD9	ENST00000221200.9	TSL:1 MANE Select	c.1146A>G	p.Leu382Leu	synonymous	Exon 12 of 12	ENSP00000221200.4
	KCTD9	ENST00000710397.1		c.1266A>G	p.Leu422Leu	synonymous	Exon 12 of 12	ENSP00000518251.1
	KCTD9	ENST00000519665.5	TSL:5	n.*1105A>G		non_coding_transcript_exon	Exon 11 of 11	ENSP00000466874.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26824 AN: 152080 Hom.: 2701 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.202 AC: 50621 AN: 250950 AF XY: 0.201

Gnomad AFR exome AF: 0.0812

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.202 AC: 288228 AN: 1427106 Hom.: 30316 Cov.: 26 AF XY: 0.201 AC XY: 143117 AN XY: 711828

African (AFR) AF: 0.0773 AC: 2542 AN: 32866

American (AMR) AF: 0.202 AC: 9029 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5332 AN: 25934

East Asian (EAS) AF: 0.211 AC: 8328 AN: 39518

South Asian (SAS) AF: 0.131 AC: 11228 AN: 85648

European-Finnish (FIN) AF: 0.227 AC: 12124 AN: 53396

Middle Eastern (MID) AF: 0.225 AC: 1233 AN: 5470

European-Non Finnish (NFE) AF: 0.210 AC: 226944 AN: 1080344

Other (OTH) AF: 0.193 AC: 11468 AN: 59278

GnomAD4 genome AF: 0.176 AC: 26835 AN: 152198 Hom.: 2706 Cov.: 32 AF XY: 0.177 AC XY: 13136 AN XY: 74408

African (AFR) AF: 0.0863 AC: 3586 AN: 41552

American (AMR) AF: 0.193 AC: 2948 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1290 AN: 5172

South Asian (SAS) AF: 0.134 AC: 648 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2366 AN: 10594

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14662 AN: 67988

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.199 Hom.: 1381

Bravo AF: 0.172

Asia WGS AF: 0.152 AC: 529 AN: 3478

EpiCase AF: 0.211

EpiControl AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.28
DANN	Benign	0.64
PhyloP100		-0.31
Mutation Taster		=98/2	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: rs1812594; hg19: chr8-25287397; COSMIC: COSV55340114; COSMIC: COSV55340114;