Variant chr9-712766-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015158.5(KANK1):c.2000G>A(p.Arg667His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,613,676 control chromosomes in the GnomAD database, including 1,241 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.027 ( 201 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1040 hom. )

Consequence

KANK1
NM_015158.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.70

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020582974).

BP6

Variant 9-712766-G-A is Benign according to our data. Variant chr9-712766-G-A is described in ClinVar as [Benign]. Clinvar id is 1166350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5 link	c.2000G>A	p.Arg667His	missense_variant	3/12	ENST00000382297.7	NP_055973.2	Q14678-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7 link	c.2000G>A	p.Arg667His	missense_variant	3/12	1	NM_015158.5	ENSP00000371734.2		Q14678-1

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4088

AN:

152096

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0821

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0248

GnomAD3 exomes

AF:

0.0380

AC:

9513

AN:

250034

Hom.:

677

AF XY:

0.0324

AC XY:

4381

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.00964

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.0257

GnomAD4 exome

AF:

0.0113

AC:

16569

AN:

1461462

Hom.:

1040

Cov.:

AF XY:

0.0105

AC XY:

7633

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.0289

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.00860

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.000734

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.0269

AC:

4088

AN:

152214

Hom.:

201

Cov.:

AF XY:

0.0303

AC XY:

2251

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.0825

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0297

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0105

Hom.:

201

Bravo

AF:

0.0333

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0331

AC:

146

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0323

AC:

3919

Asia WGS

AF:

0.106

AC:

369

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 05, 2019	This variant is associated with the following publications: (PMID: 23263489) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0030

DANN

Benign

0.88

DEOGEN2

Benign

0.0096

T;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.70

.;T;.;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.43

N;N;N;.

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.16

N;.;N;N

REVEL

Benign

0.17

Sift

Benign

0.43

T;.;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.039

ClinPred

0.0055

GERP RS

-12

Varity_R

0.015

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over