dbSNP rs201014766: NCAN:p.Thr30Asn (chr19-19218930-C-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_004386.3(NCAN):c.89C>A(p.Thr30Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,520,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

NCAN
NM_004386.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.331

Publications

0 publications found

Variant links:

Genes affected

NCAN (HGNC:2465): (neurocan) Neurocan is a chondroitin sulfate proteoglycan thought to be involved in the modulation of cell adhesion and migration.[supplied by OMIM, Jul 2002]

NCAN 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=0.035963893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004386.3. 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
	NCAN	NM_004386.3	MANE Select	c.89C>A	p.Thr30Asn	missense	Exon 3 of 15	NP_004377.2	O14594

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAN	ENST00000252575.11	TSL:1 MANE Select	c.89C>A	p.Thr30Asn	missense	Exon 3 of 15	ENSP00000252575.4	O14594
NCAN	ENST00000910091.1		c.89C>A	p.Thr30Asn	missense	Exon 4 of 16	ENSP00000580150.1
NCAN	ENST00000952495.1		c.89C>A	p.Thr30Asn	missense	Exon 3 of 15	ENSP00000622554.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000106

AC:

AN:

179542

AF XY:

0.000137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000671

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000350

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1368244

Hom.:

Cov.:

AF XY:

0.0000239

AC XY:

AN XY:

670264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30592

American (AMR)

AF:

0.000665

AC:

AN:

31578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20412

East Asian (EAS)

AF:

0.00

AC:

AN:

38382

South Asian (SAS)

AF:

0.00

AC:

AN:

71012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49696

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1064886

Other (OTH)

AF:

0.0000355

AC:

AN:

56356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000657

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41582

American (AMR)

AF:

0.000458

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000873

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.000108

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

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.9

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.22

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.34

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.34

PhyloP100

0.33

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

REVEL

Benign

0.17

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.034

Polyphen

0.14

Vest4

0.15

MutPred

0.45

Gain of sheet (P = 0.0149)

MVP

0.66

MPC

0.46

ClinPred

0.039

GERP RS

2.1

Varity_R

0.13

gMVP

0.27

Mutation Taster

=89/11

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