Variant 19-8333092-C-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.1858G>T(p.Asp620Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,612,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

KANK3
NM_198471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

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:

Genome browser will be placed here

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.1858G>T	p.Asp620Tyr	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.1858G>T	p.Asp620Tyr	missense_variant	7/11	1	NM_198471.3	ENSP00000328923	P2	Q6NY19-2
KANK3	ENST00000593649.5 linkuse as main transcript	c.1858G>T	p.Asp620Tyr	missense_variant	7/11	1		ENSP00000470728	A2	Q6NY19-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000479

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

248740

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.000501

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460476

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000184

AC:

AN:

151822

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.000653

Gnomad4 AMR

AF:

0.00

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:

0.000479

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Nov 12, 2021

The c.1858G>T (p.D620Y) alteration is located in exon 7 (coding exon 6) of the KANK3 gene. This alteration results from a G to T substitution at nucleotide position 1858, causing the aspartic acid (D) at amino acid position 620 to be replaced by a tyrosine (Y). 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

0.97

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Uncertain

0.0093

MutationAssessor

Pathogenic

3.1

M;M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-7.8

D;.;.

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.84

MVP

0.91

ClinPred

0.96

GERP RS

4.8

Varity_R

0.32

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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