Variant 19-8324733-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000330915.7(KANK3):c.2180C>A(p.Ala727Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

KANK3
ENST00000330915.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

KANK3 (HGNC:24796): (KN motif and ankyrin repeat domains 3) Predicted to be involved in negative regulation of actin filament polymerization. Predicted to be active in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

KANK3 links:

KANK3 (HGNC:):

KANK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021584928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK3	NM_198471.3 linkuse as main transcript	c.2180C>A	p.Ala727Glu	missense_variant	9/11	ENST00000330915.7	NP_940873.2	Q6NY19-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK3	ENST00000330915.7 linkuse as main transcript	c.2180C>A	p.Ala727Glu	missense_variant	9/11	1	NM_198471.3	ENSP00000328923.2		Q6NY19-2
KANK3	ENST00000593649.5 linkuse as main transcript	c.2180C>A	p.Ala727Glu	missense_variant	9/11	1		ENSP00000470728.1		Q6NY19-1

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000718

AC:

AN:

250796

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.2180C>A (p.A727E) alteration is located in exon 9 (coding exon 8) of the KANK3 gene. This alteration results from a C to A substitution at nucleotide position 2180, causing the alanine (A) at amino acid position 727 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.1

DANN

Benign

0.76

DEOGEN2

Benign

0.0019

.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.17

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

2.2

N;.

REVEL

Benign

0.078

Sift

Benign

0.52

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.12

B;.

Vest4

0.26

MutPred

0.35

Gain of solvent accessibility (P = 0.0246);Gain of solvent accessibility (P = 0.0246);

MVP

0.59

ClinPred

0.083

GERP RS

3.6

Varity_R

0.12

gMVP

0.40

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