Genetic Variant KNCN:p.Val107Met (chr1-46547786-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001322255.2(KNCN):c.319G>A(p.Val107Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,464,382 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V107E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

KNCN
NM_001322255.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061154455).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322255.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KNCN	NM_001322255.2	MANE Select	c.319G>A	p.Val107Met	missense	Exon 4 of 4	NP_001309184.1	A6PVL3-1
KNCN	NM_001097611.1		c.250G>A	p.Val84Met	missense	Exon 3 of 3	NP_001091080.1	A6PVL3-2
MKNK1-AS1	NR_038403.1		n.254+4018C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KNCN	ENST00000481882.7	TSL:5 MANE Select	c.319G>A	p.Val107Met	missense	Exon 4 of 4	ENSP00000419705.3	A6PVL3-1
KNCN	ENST00000294445.7	TSL:1	n.178G>A		non_coding_transcript_exon	Exon 3 of 3
KNCN	ENST00000396314.3	TSL:4	c.250G>A	p.Val84Met	missense	Exon 3 of 3	ENSP00000379607.3	A6PVL3-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000177

AC:

AN:

84856

AF XY:

0.000142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000216

Gnomad FIN exome

AF:

0.000904

Gnomad NFE exome

AF:

0.0000579

Gnomad OTH exome

AF:

0.000421

GnomAD4 exome

AF:

0.0000587

AC:

AN:

1312188

Hom.:

Cov.:

AF XY:

0.0000642

AC XY:

AN XY:

638208

show subpopulations

African (AFR)

AF:

0.000174

AC:

AN:

28690

American (AMR)

AF:

0.00

AC:

AN:

21288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19138

East Asian (EAS)

AF:

0.000113

AC:

AN:

35496

South Asian (SAS)

AF:

0.0000782

AC:

AN:

63946

European-Finnish (FIN)

AF:

0.000889

AC:

AN:

45000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.0000211

AC:

AN:

1040514

Other (OTH)

AF:

0.0000185

AC:

AN:

54150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000281

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.85

M_CAP

Benign

0.017

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.79

PhyloP100

3.3

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.40

MVP

0.030

MPC

0.45

ClinPred

0.29

GERP RS

3.5

Varity_R

0.35

gMVP

0.27

Mutation Taster

=94/6

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over