chr9-740769-CTTTTTT-C

Position:

• chr9-740769-CTTTTTT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_015158.5(KANK1):​c.3554-10_3554-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (7923 hom., cov: 0)
  • Exomes 𝑓: 0.30 (17032 hom.)
  • Failed GnomAD Quality Control
• Consequence: KANK1 NM_015158.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.735

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-740769-CTTTTTT-C is Benign according to our data. Variant chr9-740769-CTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 446056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-10_3554-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.3554-10_3554-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 48269 AN: 144644 Hom.: 7927 Cov.: 0

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.304

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.299 AC: 403410 AN: 1351196 Hom.: 17032 AF XY: 0.299 AC XY: 201157 AN XY: 671786

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.334 AC: 48262 AN: 144692 Hom.: 7923 Cov.: 0 AF XY: 0.330 AC XY: 23122 AN XY: 70078

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.302

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 19, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2019	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58169581; hg19: chr9-740769;