chr9-740769-C-CTTTTT

Variant names:

• chr9-740769-C-CTTTTT
• rs58169581
• NM_015158.5:c.3554-9_3554-5dupTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015158.5(KANK1):​c.3554-9_3554-5dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: KANK1 NM_015158.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.3554-9_3554-5dupTTTTT		splice_region intron	N/A	NP_055973.2	Q14678-1
	KANK1	NM_001256876.3		c.3554-9_3554-5dupTTTTT		splice_region intron	N/A	NP_001243805.1	Q14678-1
	KANK1	NM_001256877.3		c.3554-9_3554-5dupTTTTT		splice_region 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.3554-23_3554-22insTTTTT		intron	N/A	ENSP00000371734.2	Q14678-1
	KANK1	ENST00000382303.5	TSL:1	c.3554-23_3554-22insTTTTT		intron	N/A	ENSP00000371740.1	Q14678-1
	KANK1	ENST00000382293.7	TSL:1	c.3080-23_3080-22insTTTTT		intron	N/A	ENSP00000371730.3	Q14678-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000514 AC: 7 AN: 1361116 Hom.: 0 Cov.: 0 AF XY: 0.00000443 AC XY: 3 AN XY: 676648

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000100 AC: 3 AN: 29956

American (AMR) AF: 0.0000297 AC: 1 AN: 33724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23404

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37944

South Asian (SAS) AF: 0.0000260 AC: 2 AN: 76900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051304

Other (OTH) AF: 0.00 AC: 0 AN: 56120

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs58169581; hg19: chr9-740769;