9-676954-T-C

Position:

• chr9-676954-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015158.5(KANK1):​c.-19T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,608,986 control chromosomes in the GnomAD database, including 64,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (13419 hom., cov: 33)
  • Exomes 𝑓: 0.24 (50941 hom.)
• Consequence: KANK1 NM_015158.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.573

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-676954-T-C is Benign according to our data. Variant chr9-676954-T-C is described in ClinVar as [Benign]. Clinvar id is 1238818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-19T>C		5_prime_UTR_variant	2/12	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-19T>C		5_prime_UTR_variant	2/12	1	NM_015158.5	ENSP00000371734	P2
	ENST00000421645.2	n.219-2575A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56933 AN: 151990 Hom.: 13386 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.328

GnomAD3 exomes AF: 0.310 AC: 77652 AN: 250636 Hom.: 14505 AF XY: 0.295 AC XY: 39919 AN XY: 135446

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.574

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.245 AC: 356813 AN: 1456876 Hom.: 50941 Cov.: 30 AF XY: 0.244 AC XY: 176536 AN XY: 724942

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.375 AC: 57006 AN: 152110 Hom.: 13419 Cov.: 33 AF XY: 0.379 AC XY: 28215 AN XY: 74360

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.334

Alfa AF: 0.301 Hom.: 2833

Bravo AF: 0.392

Asia WGS AF: 0.481 AC: 1669 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296055; hg19: chr9-676954; COSMIC: COSV63210971;