9-676571-T-C

Variant names:

• chr9-676571-T-C
• rs9407353
• NM_015158.5:c.-83-319T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015158.5(KANK1):​c.-83-319T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,248 control chromosomes in the GnomAD database, including 2,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2943 hom., cov: 32)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300
• 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), G2P, Ambry Genetics

ENSG00000227914 (HGNC:58139):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-676571-T-C is Benign according to our data. Variant chr9-676571-T-C is described in ClinVar as [Benign]. Clinvar id is 1281222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-83-319T>C		intron_variant	Intron 1 of 11	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-319T>C		intron_variant	Intron 1 of 11	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27142 AN: 152130 Hom.: 2940 Cov.: 32

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.178 AC: 27145 AN: 152248 Hom.: 2943 Cov.: 32 AF XY: 0.179 AC XY: 13314 AN XY: 74438

African (AFR) AF: 0.0485 AC: 2015 AN: 41548

American (AMR) AF: 0.192 AC: 2942 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5182

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4830

European-Finnish (FIN) AF: 0.210 AC: 2230 AN: 10604

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15861 AN: 68000

Other (OTH) AF: 0.195 AC: 412 AN: 2116

Alfa AF: 0.196 Hom.: 441

Bravo AF: 0.173

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.76
PhyloP100		0.030
PromoterAI		-0.0072	Neutral
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: rs9407353; hg19: chr9-676571; COSMIC: COSV63215309;