Variant chr10-133186204-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000304613.8(KNDC1):c.856G>A(p.Glu286Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,572,904 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 27 hom. )

Consequence

KNDC1
ENST00000304613.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.350

Variant links:

Genes affected

KNDC1 (HGNC:29374): (kinase non-catalytic C-lobe domain containing 1) The protein encoded by this gene is a Ras guanine nucleotide exchange factor that appears to negatively regulate dendritic growth in the brain. Knockdown of this gene in senescent umbilical vein endothelial cells partially reversed the senescence, showing that this gene could potentially be targeted by anti-aging therapies. [provided by RefSeq, Dec 2016]

KNDC1 links:

KNDC1 (HGNC:):

KNDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003722906).

BP6

Variant 10-133186204-G-A is Benign according to our data. Variant chr10-133186204-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3257617.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNDC1	NM_152643.8 linkuse as main transcript	c.856G>A	p.Glu286Lys	missense_variant	6/30	ENST00000304613.8	NP_689856.6	Q76NI1-1
KNDC1	XM_017016858.3 linkuse as main transcript	c.856G>A	p.Glu286Lys	missense_variant	6/27		XP_016872347.1
KNDC1	XM_017016859.3 linkuse as main transcript	c.856G>A	p.Glu286Lys	missense_variant	6/21		XP_016872348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNDC1	ENST00000304613.8 linkuse as main transcript	c.856G>A	p.Glu286Lys	missense_variant	6/30	1	NM_152643.8	ENSP00000304437.3		Q76NI1-1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

393

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00961

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00399

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00316

AC:

608

AN:

192244

Hom.:

AF XY:

0.00327

AC XY:

346

AN XY:

105952

show subpopulations

Gnomad AFR exome

AF:

0.000171

Gnomad AMR exome

AF:

0.000277

Gnomad ASJ exome

AF:

0.000450

Gnomad EAS exome

AF:

0.0000630

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.00417

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

AF:

0.00198

AC:

2820

AN:

1420678

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1441

AN XY:

702944

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

Gnomad4 AMR exome

AF:

0.000325

Gnomad4 ASJ exome

AF:

0.000211

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00188

Gnomad4 OTH exome

AF:

0.00173

GnomAD4 genome

AF:

0.00258

AC:

393

AN:

152226

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00961

Gnomad4 NFE

AF:

0.00399

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00315

Hom.:

Bravo

AF:

0.00119

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00282

AC:

ExAC

AF:

0.00318

AC:

382

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

KNDC1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.4

DANN

Benign

0.52

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.34

N;N

REVEL

Benign

0.015

Sift

Benign

0.74

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;B

Vest4

0.069

MVP

0.048

MPC

0.21

ClinPred

0.0013

GERP RS

-2.9

Varity_R

0.035

gMVP

0.21

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