Variant 1-62238374-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_181712.5(KANK4):c.2891G>A(p.Arg964His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,634 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

KANK4
NM_181712.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0330

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008780092).

BP6

Variant 1-62238374-C-T is Benign according to our data. Variant chr1-62238374-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1583742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK4	NM_181712.5 linkuse as main transcript	c.2891G>A	p.Arg964His	missense_variant	10/10	ENST00000371153.9	NP_859063.3	Q5T7N3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KANK4	ENST00000371153.9 linkuse as main transcript	c.2891G>A	p.Arg964His	missense_variant	10/10	1	NM_181712.5	ENSP00000360195.4	Q5T7N3-1
KANK4	ENST00000354381.3 linkuse as main transcript	c.1007G>A	p.Arg336His	missense_variant	9/9	2		ENSP00000346352.3	Q5T7N3-2
KANK4	ENST00000371150.5 linkuse as main transcript	c.959G>A	p.Arg320His	missense_variant	7/7	2		ENSP00000360192.1	B1ALP6
KANK4	ENST00000317477.8 linkuse as main transcript	c.305G>A	p.Arg102His	missense_variant	4/4	2		ENSP00000321161.4	B1ALP5

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00502

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00113

AC:

283

AN:

249706

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.000683

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00534

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00145

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.00162

AC:

2370

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1102

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00358

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00190

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152212

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00484

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00115

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00115

AC:

140

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

KANK4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 28, 2021

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

Benign

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0084

T;T;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.90

D;T;T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

.;L;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.62

N;N;N;N

REVEL

Benign

0.045

Sift

Uncertain

0.017

D;T;D;D

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.0080, 0.0010

.;B;.;B

Vest4

0.042

MVP

0.24

MPC

0.53

ClinPred

0.034

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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