ENST00000718394.1:n.*189+2189T>C

Variant names:

• chr9-21327142-A-G
• rs913931
• ENST00000718394.1:n.*189+2189T>C

Variant summary

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

The ENST00000718394.1(KLHL9):​n.*189+2189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,148 control chromosomes in the GnomAD database, including 1,268 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 0.13 (1268 hom., cov: 32)
• Consequence: KLHL9 ENST00000718394.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 8 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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107987053	XR_001746634.2	n.472-9479A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL9	ENST00000718394.1	n.*189+2189T>C		intron_variant	Intron 2 of 3			ENSP00000520799.1
KLHL9	ENST00000718395.1	n.*101-2821T>C		intron_variant	Intron 1 of 1			ENSP00000520800.1
ENSG00000301340	ENST00000778316.1	n.385-9479A>G		intron_variant	Intron 2 of 2
ENSG00000301340	ENST00000778317.1	n.539-9479A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19563 AN: 152030 Hom.: 1267 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.129 AC: 19580 AN: 152148 Hom.: 1268 Cov.: 32 AF XY: 0.128 AC XY: 9535 AN XY: 74386

African (AFR) AF: 0.127 AC: 5291 AN: 41520

American (AMR) AF: 0.109 AC: 1665 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3468

East Asian (EAS) AF: 0.102 AC: 527 AN: 5178

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4816

European-Finnish (FIN) AF: 0.102 AC: 1076 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9141 AN: 67964

Other (OTH) AF: 0.129 AC: 272 AN: 2112

Alfa AF: 0.130 Hom.: 2425

Bravo AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.0
DANN	Benign	0.92
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs913931; hg19: chr9-21327141;