rs145623004

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_181712.5(KANK4):c.2401T>C(p.Tyr801His) variant causes a missense change. The variant allele was found at a frequency of 0.00115 in 1,613,918 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 9 hom. )

Consequence

KANK4
NM_181712.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts P:1U:1B:4

Conservation

PhyloP100: 6.93

Publications

8 publications found

Variant links:

Genes affected

KANK4 (HGNC:27263): (KN motif and ankyrin repeat domains 4) Predicted to be involved in negative regulation of actin filament polymerization. Located in cytosol and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

KANK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0119796395).

BP6

Variant 1-62263230-A-G is Benign according to our data. Variant chr1-62263230-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 446389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK4	NM_181712.5 link	c.2401T>C	p.Tyr801His	missense_variant	Exon 7 of 10	ENST00000371153.9	NP_859063.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KANK4	ENST00000371153.9 link	c.2401T>C	p.Tyr801His	missense_variant	Exon 7 of 10	1	NM_181712.5	ENSP00000360195.4
KANK4	ENST00000354381.3 link	c.517T>C	p.Tyr173His	missense_variant	Exon 6 of 9	2		ENSP00000346352.3
KANK4	ENST00000371150.5 link	c.469T>C	p.Tyr157His	missense_variant	Exon 4 of 7	2		ENSP00000360192.1
KANK4	ENST00000317477.8 link	c.-186T>C		5_prime_UTR_variant	Exon 1 of 4	2		ENSP00000321161.4

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00112

AC:

281

AN:

250780

AF XY:

0.000937

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.00114

AC:

1665

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

851

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33472

American (AMR)

AF:

0.00143

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

128

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.000786

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00119

AC:

1325

AN:

1111924

Other (OTH)

AF:

0.00149

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152242

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41544

American (AMR)

AF:

0.00216

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000566

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

68022

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00130

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000997

AC:

121

EpiCase

AF:

0.00196

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2017

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KANK4: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nephrotic syndrome

Pathogenic:1

Nov 10, 2017

Yale Center for Mendelian Genomics, Yale University

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

KANK4-related disorder

Benign:1

Apr 01, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

T;T;T

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.2

M;.;.

PhyloP100

6.9

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.7

D;D;N

REVEL

Benign

0.26

Sift

Benign

0.13

T;T;T

Sift4G

Uncertain

0.0020

D;T;T

Polyphen

0.053

B;.;D

Vest4

0.45

MVP

0.49

MPC

0.14

ClinPred

0.031

GERP RS

5.3

PromoterAI

0.041

Neutral

(source)

Varity_R

0.19

gMVP

0.69

Mutation Taster

=6/94

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over