Genetic Variant KNCN:p.Arg101Leu (chr1-46547803-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001322255.2(KNCN):c.302G>T(p.Arg101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,118 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

KNCN
NM_001322255.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

1 publications found

Variant links:

Genes affected

KNCN (HGNC:26488): (kinocilin) Predicted to be located in apical part of cell; cytoplasm; and microtubule cytoskeleton. Predicted to be active in several cellular components, including apical plasma membrane; cytoskeleton; and kinocilium. [provided by Alliance of Genome Resources, Apr 2022]

KNCN links:

MKNK1-AS1 (HGNC:44129): (MKNK1 antisense RNA 1)

MKNK1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15538359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KNCN	NM_001322255.2 link	c.302G>T	p.Arg101Leu	missense_variant	Exon 4 of 4	ENST00000481882.7	NP_001309184.1	A6PVL3-1
KNCN	NM_001097611.1 link	c.233G>T	p.Arg78Leu	missense_variant	Exon 3 of 3		NP_001091080.1	A6PVL3-2
MKNK1-AS1	NR_038403.1 link	n.254+4035C>A		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KNCN	ENST00000481882.7 link	c.302G>T	p.Arg101Leu	missense_variant	Exon 4 of 4	5	NM_001322255.2	ENSP00000419705.3		A6PVL3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

80558

AF XY:

0.0000250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000311

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.66e-7

AC:

AN:

1305118

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

633672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28456

American (AMR)

AF:

0.00

AC:

AN:

20304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18972

East Asian (EAS)

AF:

0.00

AC:

AN:

35244

South Asian (SAS)

AF:

0.00

AC:

AN:

63374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3736

European-Non Finnish (NFE)

AF:

9.65e-7

AC:

AN:

1036430

Other (OTH)

AF:

0.00

AC:

AN:

53800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

0.0090

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.83

PhyloP100

1.7

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.025

D;D

Sift4G

Uncertain

0.042

D;T

Polyphen

0.18

.;B

Vest4

0.43

MutPred

0.17

.;Loss of MoRF binding (P = 0.0019);

MVP

0.11

MPC

0.12

ClinPred

0.78

GERP RS

2.5

Varity_R

0.21

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-46547803-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over