9-603192-T-G

Variant names:

• chr9-603192-T-G
• rs1532309
• NM_015158.5:c.-83-73698T>G

Variant summary

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

The NM_015158.5(KANK1):​c.-83-73698T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,710 control chromosomes in the GnomAD database, including 12,636 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 0.37 (12636 hom., cov: 32)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 6 publications found

Genes affected

KANK1 (HGNC:19309): (KN motif and ankyrin repeat domains 1) The protein encoded by this gene belongs to the Kank family of proteins, which contain multiple ankyrin repeat domains. This family member functions in cytoskeleton formation by regulating actin polymerization. This gene is a candidate tumor suppressor for renal cell carcinoma. Mutations in this gene cause cerebral palsy spastic quadriplegic type 2, a central nervous system development disorder. A t(5;9) translocation results in fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) on chromosome 5 with this gene in a myeloproliferative neoplasm featuring severe thrombocythemia. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2014]

KANK1 Gene-Disease associations (from GenCC):

• spastic quadriplegic cerebral palsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy, spastic quadriplegic, 2

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015158.5. 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
	KANK1	NM_015158.5	MANE Select	c.-83-73698T>G		intron	N/A	NP_055973.2	Q14678-1
	KANK1	NM_001256876.3		c.-84+62525T>G		intron	N/A	NP_001243805.1	Q14678-1
	KANK1	NM_001256877.3		c.-84+53471T>G		intron	N/A	NP_001243806.1	Q14678-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	ENST00000382297.7	TSL:1 MANE Select	c.-83-73698T>G		intron	N/A	ENSP00000371734.2	Q14678-1
	KANK1	ENST00000382303.5	TSL:1	c.-84+62525T>G		intron	N/A	ENSP00000371740.1	Q14678-1
	KANK1	ENST00000619269.5	TSL:5	c.-83-73698T>G		intron	N/A	ENSP00000477725.2	A0A8J9BYE6

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55721 AN: 151596 Hom.: 12641 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.367 AC: 55701 AN: 151710 Hom.: 12636 Cov.: 32 AF XY: 0.367 AC XY: 27175 AN XY: 74144

African (AFR) AF: 0.140 AC: 5779 AN: 41154

American (AMR) AF: 0.312 AC: 4768 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1574 AN: 3470

East Asian (EAS) AF: 0.0998 AC: 517 AN: 5180

South Asian (SAS) AF: 0.566 AC: 2724 AN: 4810

European-Finnish (FIN) AF: 0.454 AC: 4802 AN: 10566

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34229 AN: 67966

Other (OTH) AF: 0.397 AC: 832 AN: 2098

Alfa AF: 0.293 Hom.: 927

Bravo AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.17
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: rs1532309; hg19: chr9-603192;