Variant chr19-8322919-C-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 NM_198471.3(KANK3):c.2386G>A(p.Glu796Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,511,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

KANK3
NM_198471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

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:

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS28 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=0.016808003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK3	NM_198471.3 link	c.2386G>A	p.Glu796Lys	missense_variant	11/11	ENST00000330915.7	NP_940873.2	Q6NY19-2
RPS28	NM_001031.5 link	c.*664C>T		3_prime_UTR_variant	4/4	ENST00000600659.3	NP_001022.1	P62857B2R4R9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KANK3	ENST00000330915.7 link	c.2386G>A	p.Glu796Lys	missense_variant	11/11	1	NM_198471.3	ENSP00000328923.2	Q6NY19-2
RPS28	ENST00000600659.3 link	c.*664C>T		3_prime_UTR_variant	4/4	1	NM_001031.5	ENSP00000472469.1	P62857
RPS28	ENST00000449223.3 link	n.1496C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000353

AC:

AN:

147136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000658

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000287

AC:

AN:

167326

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

90748

show subpopulations

Gnomad AFR exome

AF:

0.0000863

Gnomad AMR exome

AF:

0.0000501

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000774

Gnomad SAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000516

Gnomad OTH exome

AF:

0.000278

GnomAD4 exome

AF:

0.000551

AC:

752

AN:

1364418

Hom.:

Cov.:

AF XY:

0.000556

AC XY:

374

AN XY:

672094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000328

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.0000938

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.000684

Gnomad4 OTH exome

AF:

0.000287

GnomAD4 genome

AF:

0.000353

AC:

AN:

147242

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

AN XY:

72004

show subpopulations

Gnomad4 AFR

AF:

0.000104

Gnomad4 AMR

AF:

0.000135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000658

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000574

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000265

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

Jun 18, 2024

The c.2386G>A (p.E796K) alteration is located in exon 11 (coding exon 10) of the KANK3 gene. This alteration results from a G to A substitution at nucleotide position 2386, causing the glutamic acid (E) at amino acid position 796 to be replaced by a lysine (K). 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

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.67

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.47

M_CAP

Benign

0.0020

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.31

PROVEAN

Benign

0.18

REVEL

Benign

0.0060

Sift

Benign

0.68

Sift4G

Benign

0.32

Polyphen

0.15

Vest4

0.18

MVP

0.12

ClinPred

0.0025

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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