Variant 19-8324481-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198471.3(KANK3):c.2350G>T(p.Ala784Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

KANK3
NM_198471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21642041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK3	NM_198471.3 link	c.2350G>T	p.Ala784Ser	missense_variant	10/11	ENST00000330915.7	NP_940873.2	Q6NY19-2
KANK3	XM_017026563.3 link	c.2503G>T	p.Ala835Ser	missense_variant	9/10		XP_016882052.1
KANK3	XM_006722718.5 link	c.2350G>T	p.Ala784Ser	missense_variant	10/11		XP_006722781.1	Q6NY19-2
KANK3	XM_011527884.2 link	c.2350G>T	p.Ala784Ser	missense_variant	10/11		XP_011526186.1	Q6NY19-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK3	ENST00000330915.7 link	c.2350G>T	p.Ala784Ser	missense_variant	10/11	1	NM_198471.3	ENSP00000328923.2		Q6NY19-2
KANK3	ENST00000593649.5 link	c.2350G>T	p.Ala784Ser	missense_variant	10/11	1		ENSP00000470728.1		Q6NY19-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

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:

0.00

ExAC

AF:

0.00000824

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

Feb 06, 2024

The c.2350G>T (p.A784S) alteration is located in exon 10 (coding exon 9) of the KANK3 gene. This alteration results from a G to T substitution at nucleotide position 2350, causing the alanine (A) at amino acid position 784 to be replaced by a serine (S). 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

0.099

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;T

Eigen

Benign

-0.015

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.087

Sift

Uncertain

0.018

D;.

Sift4G

Benign

0.22

T;T

Polyphen

1.0

D;.

Vest4

0.41

MutPred

0.22

Gain of glycosylation at A784 (P = 0.0211);Gain of glycosylation at A784 (P = 0.0211);

MVP

0.62

ClinPred

0.68

GERP RS

3.7

Varity_R

0.059

gMVP

0.23

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