Genetic Variant NM_020223.4:c.155C>T (chr7-193354-C-T) – 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_020223.4(FAM20C):c.155C>T(p.Ala52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000893 in 1,119,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

FAM20C
NM_020223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.489

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:

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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=0.18227562).

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.155C>T	p.Ala52Val	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.155C>T	p.Ala52Val	missense	Exon 1 of 10	ENSP00000322323.5	Q8IXL6-1
FAM20C	ENST00000942064.1		c.155C>T	p.Ala52Val	missense	Exon 1 of 11	ENSP00000612123.1
FAM20C	ENST00000866115.1		c.155C>T	p.Ala52Val	missense	Exon 1 of 11	ENSP00000536174.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.93e-7

AC:

AN:

1119444

Hom.:

Cov.:

AF XY:

0.00000184

AC XY:

AN XY:

543058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21846

American (AMR)

AF:

0.00

AC:

AN:

8574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13914

East Asian (EAS)

AF:

0.00

AC:

AN:

23034

South Asian (SAS)

AF:

0.00

AC:

AN:

35826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3412

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

941522

Other (OTH)

AF:

0.00

AC:

AN:

43514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.41

PhyloP100

0.49

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Benign

0.059

Sift4G

Benign

0.065

Polyphen

0.14

Vest4

0.073

MutPred

0.32

Gain of stability (P = 0.0818)

MVP

0.17

MPC

0.63

ClinPred

0.12

GERP RS

2.8

Varity_R

0.082

gMVP

0.44

Mutation Taster

=90/10

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