dbSNP rs200004606: KNDC1:p.Val210Ile (chr10-133185976-G-A) – 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_152643.8(KNDC1):c.628G>A(p.Val210Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,592,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

KNDC1
NM_152643.8 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.292

Publications

0 publications found

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:

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=0.0063857436).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152643.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNDC1	NM_152643.8	MANE Select	c.628G>A	p.Val210Ile	missense splice_region	Exon 6 of 30	NP_689856.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KNDC1	ENST00000304613.8	TSL:1 MANE Select	c.628G>A	p.Val210Ile	missense splice_region	Exon 6 of 30	ENSP00000304437.3	Q76NI1-1
KNDC1	ENST00000368571.3	TSL:1	c.628G>A	p.Val210Ile	missense splice_region	Exon 6 of 17	ENSP00000357560.3	Q76NI1-4
KNDC1	ENST00000946348.1		c.628G>A	p.Val210Ile	missense splice_region	Exon 6 of 31	ENSP00000616407.1

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00117

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

GnomAD2 exomes

AF:

0.0000633

AC:

AN:

205470

AF XY:

0.0000267

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000744

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1441248

Hom.:

Cov.:

AF XY:

0.00000979

AC XY:

AN XY:

714802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

41948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25466

East Asian (EAS)

AF:

0.000538

AC:

AN:

39030

South Asian (SAS)

AF:

0.00

AC:

AN:

82768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103888

Other (OTH)

AF:

0.0000168

AC:

AN:

59634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000396

AC:

AN:

151414

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41104

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00118

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67798

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000683

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000758

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

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

0.071

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.9

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.053

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.50

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.99

PhyloP100

-0.29

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.14

REVEL

Benign

0.047

Sift

Benign

0.27

Sift4G

Benign

0.25

Polyphen

0.0010

Vest4

0.080

MVP

0.088

MPC

0.15

ClinPred

0.023

GERP RS

-4.0

Varity_R

0.037

gMVP

0.14

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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