Variant chr19-8333215-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198471.3(KANK3):c.1735G>A(p.Val579Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,611,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KANK3
NM_198471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.07

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK3	NM_198471.3 link	c.1735G>A	p.Val579Met	missense_variant	7/11	ENST00000330915.7	NP_940873.2	Q6NY19-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KANK3	ENST00000330915.7 link	c.1735G>A	p.Val579Met	missense_variant	7/11	1	NM_198471.3	ENSP00000328923.2	Q6NY19-2
KANK3	ENST00000593649.5 link	c.1735G>A	p.Val579Met	missense_variant	7/11	1		ENSP00000470728.1	Q6NY19-1
KANK3	ENST00000595639.1 link	c.*2G>A		downstream_gene_variant		5		ENSP00000470585.1	M0QZJ3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

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:

0.000478

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

243548

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133074

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1458888

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725760

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000105

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000907

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Nov 13, 2023

The c.1735G>A (p.V579M) alteration is located in exon 7 (coding exon 6) of the KANK3 gene. This alteration results from a G to A substitution at nucleotide position 1735, causing the valine (V) at amino acid position 579 to be replaced by a methionine (M). 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.8

N;.;.

REVEL

Benign

0.23

Sift

Uncertain

0.0030

D;.;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.77

MutPred

0.42

Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;

MVP

0.71

ClinPred

0.66

GERP RS

4.5

Varity_R

0.10

gMVP

0.36

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