dbSNP rs1177102899: FAM20C:p.Ala26Pro (chr7-193275-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020223.4(FAM20C):c.76G>C(p.Ala26Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,448,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

FAM20C
NM_020223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.954

Publications

0 publications found

Variant links:

Genes affected

FAM20C (HGNC:22140): (FAM20C golgi associated secretory pathway kinase) This gene encodes a member of the family of secreted protein kinases. The encoded protein binds calcium and phosphorylates proteins involved in bone mineralization. Mutations in this gene are associated with the autosomal recessive disorder Raine syndrome. [provided by RefSeq, Apr 2014]

FAM20C Gene-Disease associations (from GenCC):

lethal osteosclerotic bone dysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

FAM20C links:

ENSG00000240093 (HGNC:):

ENSG00000240093 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020223.4. 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
	FAM20C	NM_020223.4	MANE Select	c.76G>C	p.Ala26Pro	missense	Exon 1 of 10	NP_064608.2	Q8IXL6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM20C	ENST00000313766.6	TSL:1 MANE Select	c.76G>C	p.Ala26Pro	missense	Exon 1 of 10	ENSP00000322323.5	Q8IXL6-1
FAM20C	ENST00000942064.1		c.76G>C	p.Ala26Pro	missense	Exon 1 of 11	ENSP00000612123.1
FAM20C	ENST00000866115.1		c.76G>C	p.Ala26Pro	missense	Exon 1 of 11	ENSP00000536174.1

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000989

AC:

AN:

101108

AF XY:

0.0000179

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:

0.0000256

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1298890

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

641200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25792

American (AMR)

AF:

0.00

AC:

AN:

29814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21636

East Asian (EAS)

AF:

0.00

AC:

AN:

27332

South Asian (SAS)

AF:

0.00

AC:

AN:

74888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5194

European-Non Finnish (NFE)

AF:

0.0000165

AC:

AN:

1029756

Other (OTH)

AF:

0.0000191

AC:

AN:

52420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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:

0.00000667

AC:

AN:

149932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73116

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41182

American (AMR)

AF:

0.00

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67258

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

0.0055

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.0096

Eigen_PC

Benign

0.00096

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.84

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.51

PhyloP100

0.95

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.44

Sift

Benign

0.038

Sift4G

Benign

0.086

Polyphen

0.83

Vest4

0.29

MutPred

0.60

Gain of loop (P = 3e-04)

MVP

0.60

MPC

0.79

ClinPred

0.23

GERP RS

3.2

Varity_R

0.19

gMVP

0.54

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over