Variant rs145623004 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:3

Conservation

PhyloP100: 6.93

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
KANK4	NM_181712.5 link	c.2401T>C	p.Tyr801His	missense_variant	7/10	ENST00000371153.9	NP_859063.3	Q5T7N3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KANK4	ENST00000371153.9 link	c.2401T>C	p.Tyr801His	missense_variant	7/10	1	NM_181712.5	ENSP00000360195.4	Q5T7N3-1
KANK4	ENST00000354381.3 link	c.517T>C	p.Tyr173His	missense_variant	6/9	2		ENSP00000346352.3	Q5T7N3-2
KANK4	ENST00000371150.5 link	c.469T>C	p.Tyr157His	missense_variant	4/7	2		ENSP00000360192.1	B1ALP6
KANK4	ENST00000317477.8 link	c.-186T>C		5_prime_UTR_variant	1/4	2		ENSP00000321161.4	B1ALP5

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

GnomAD3 exomes

AF:

0.00112

AC:

281

AN:

250780

Hom.:

AF XY:

0.000937

AC XY:

127

AN XY:

135590

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 SAS 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

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152242

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00166

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, no assertion criteria provided	literature only	OMIM	Nov 27, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 09, 2024	- -

Nephrotic syndrome

Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

Nov 10, 2017

- -

KANK4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2022

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

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;.;.

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

Varity_R

0.19

gMVP

0.69

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