Variant 19-8333026-G-A 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.1924C>T(p.Leu642Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,259,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

KANK3
NM_198471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

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 linkuse as main transcript	c.1924C>T	p.Leu642Phe	missense_variant	7/11	ENST00000330915.7	NP_940873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK3	ENST00000330915.7 linkuse as main transcript	c.1924C>T	p.Leu642Phe	missense_variant	7/11	1	NM_198471.3	ENSP00000328923	P2	Q6NY19-2
KANK3	ENST00000593649.5 linkuse as main transcript	c.1924C>T	p.Leu642Phe	missense_variant	7/11	1		ENSP00000470728	A2	Q6NY19-1

Frequencies

GnomAD3 genomes

AF:

0.000433

AC:

AN:

138676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000223

Gnomad ASJ

AF:

0.00149

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000724

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000619

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000275

AC:

AN:

240300

Hom.:

AF XY:

0.000298

AC XY:

AN XY:

130680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.000814

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000443

Gnomad NFE exome

AF:

0.000410

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000708

AC:

794

AN:

1121044

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

380

AN XY:

559018

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00148

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.000823

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000432

AC:

AN:

138776

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

AN XY:

66952

show subpopulations

Gnomad4 AFR

AF:

0.000157

Gnomad4 AMR

AF:

0.000222

Gnomad4 ASJ

AF:

0.00149

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000724

Gnomad4 NFE

AF:

0.000619

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000587

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000165

AC:

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

Dec 13, 2022

The c.1924C>T (p.L642F) alteration is located in exon 7 (coding exon 6) of the KANK3 gene. This alteration results from a C to T substitution at nucleotide position 1924, causing the leucine (L) at amino acid position 642 to be replaced by a phenylalanine (F). 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

0.86

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

.;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Uncertain

0.44

MutationAssessor

Uncertain

2.9

M;M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.4

D;.;.

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.65

MVP

0.95

ClinPred

0.38

GERP RS

4.8

Varity_R

0.079

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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