9-710915-A-T

Position:

chr9-710915-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153186.6(KANK1):c.-326A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00859 in 1,614,174 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 76 hom. )

Consequence

KANK1
NM_153186.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 8.84

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:

KANK1 (HGNC:):

KANK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012142837).

BP6

Variant 9-710915-A-T is Benign according to our data. Variant chr9-710915-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 377350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-710915-A-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 907 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5 linkuse as main transcript	c.149A>T	p.Asp50Val	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 linkuse as main transcript	c.149A>T	p.Asp50Val	missense_variant	3/12	1	NM_015158.5	ENSP00000371734.2		Q14678-1

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

908

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00969

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00565

AC:

1420

AN:

251486

Hom.:

AF XY:

0.00561

AC XY:

762

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.00993

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00887

AC:

12960

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

6208

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.00596

AC:

907

AN:

152302

Hom.:

Cov.:

AF XY:

0.00507

AC XY:

378

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00967

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00709

Hom.:

Bravo

AF:

0.00634

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00977

AC:

ExAC

AF:

0.00607

AC:

737

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00878

EpiControl

AF:

0.00723

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	KANK1: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 28, 2016	- -

Amyotrophic lateral sclerosis

Uncertain:1

Uncertain significance, no assertion criteria provided

research

UM ALS/MND Lab, University Of Malta

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.56

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

.;D;.

M_CAP

Benign

0.053

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.6

D;.;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.77

MVP

0.71

ClinPred

0.027

GERP RS

6.0

Varity_R

0.94

gMVP

0.34

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