rs8729

Variant names:

• chr9-21331120-C-T
• rs8729
• NM_018847.4:c.*1886G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018847.4(KLHL9):​c.*1886G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,352 control chromosomes in the GnomAD database, including 5,608 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 0.26 (5601 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7 hom.)
• Consequence: KLHL9 NM_018847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 17 publications found

Genes affected

KLHL9 (HGNC:18732): (kelch like family member 9) This gene encodes a protein that belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain, a BACK domain and six C-terminal kelch repeats. The encoded protein is a component of a complex with cullin 3-based E3 ligase, which plays a role in mitosis. This protein complex is a cell cycle regulator, and functions in the organization and integrity of the spindle midzone in anaphase and the completion of cytokinesis. The complex is required for the removal of the chromosomal passenger protein aurora B from mitotic chromosomes. [provided by RefSeq, Jul 2016]

KLHL9 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000301340 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018847.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL9	NM_018847.4	MANE Select	c.*1886G>A		3_prime_UTR	Exon 1 of 1	NP_061335.1	Q9P2J3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL9	ENST00000359039.5	TSL:6 MANE Select	c.*1886G>A		3_prime_UTR	Exon 1 of 1	ENSP00000351933.4	Q9P2J3
	KLHL9	ENST00000718394.1		n.*101-1701G>A		intron	N/A	ENSP00000520799.1	Q9P2J3
	KLHL9	ENST00000718395.1		n.*100+1786G>A		intron	N/A	ENSP00000520800.1	Q9P2J3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39844 AN: 151804 Hom.: 5592 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.179 AC: 77 AN: 430 Hom.: 7 Cov.: 0 AF XY: 0.171 AC XY: 44 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.182 AC: 77 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.263 AC: 39894 AN: 151922 Hom.: 5601 Cov.: 32 AF XY: 0.262 AC XY: 19438 AN XY: 74258

African (AFR) AF: 0.337 AC: 13947 AN: 41404

American (AMR) AF: 0.310 AC: 4731 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 827 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2139 AN: 5176

South Asian (SAS) AF: 0.163 AC: 784 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2207 AN: 10536

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14494 AN: 67942

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.254 Hom.: 2096

Bravo AF: 0.278

Asia WGS AF: 0.299 AC: 1036 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.70
PhyloP100		-0.36
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs8729;

hg19: chr9-21331119;