NM_017634.4:c.1146A>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017634.4(KCTD9):​c.1146A>C​(p.Leu382Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.311 with no splicing effect.

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>C	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>C	p.Leu382Leu	synonymous	Exon 12 of 12	ENSP00000221200.4
	KCTD9	ENST00000710397.1		c.1266A>C	p.Leu422Leu	synonymous	Exon 12 of 12	ENSP00000518251.1
	KCTD9	ENST00000519665.5	TSL:5	n.*1105A>C		non_coding_transcript_exon	Exon 11 of 11	ENSP00000466874.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250950 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431026 Hom.: 0 Cov.: 26 AF XY: 0.00000140 AC XY: 1 AN XY: 713622

African (AFR) AF: 0.00 AC: 0 AN: 32894

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 85700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083984

Other (OTH) AF: 0.00 AC: 0 AN: 59396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.21
DANN	Benign	0.65
PhyloP100		-0.31

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;