rs36170987

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020223.4(FAM20C):c.1659G>T(p.Val553Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,535,618 control chromosomes in the GnomAD database, including 166,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21881 hom., cov: 35)

Exomes 𝑓: 0.45 ( 144829 hom. )

Consequence

FAM20C
NM_020223.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0870

Publications

14 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: G2P, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

FAM20C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 7-259884-G-T is Benign according to our data. Variant chr7-259884-G-T is described in ClinVar as Benign. ClinVar VariationId is 193730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20C	NM_020223.4 link	c.1659G>T	p.Val553Val	synonymous_variant	Exon 10 of 10	ENST00000313766.6	NP_064608.2	Q8IXL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6 link	c.1659G>T	p.Val553Val	synonymous_variant	Exon 10 of 10	1	NM_020223.4	ENSP00000322323.5		Q8IXL6-1
FAM20C	ENST00000515795.1 link	n.1316G>T		non_coding_transcript_exon_variant	Exon 7 of 7	1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79666

AN:

152036

Hom.:

21840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.695

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.460

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.438

AC:

61566

AN:

140424

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.703

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.453

AC:

626956

AN:

1383464

Hom.:

144829

Cov.:

AF XY:

0.452

AC XY:

308680

AN XY:

682612

show subpopulations

African (AFR)

AF:

0.701

AC:

22129

AN:

31586

American (AMR)

AF:

0.272

AC:

9695

AN:

35672

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

11602

AN:

25156

East Asian (EAS)

AF:

0.475

AC:

16969

AN:

35702

South Asian (SAS)

AF:

0.437

AC:

34628

AN:

79188

European-Finnish (FIN)

AF:

0.526

AC:

17978

AN:

34158

Middle Eastern (MID)

AF:

0.489

AC:

2775

AN:

5680

European-Non Finnish (NFE)

AF:

0.449

AC:

484009

AN:

1078448

Other (OTH)

AF:

0.469

AC:

27171

AN:

57874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

21940

43880

65820

87760

109700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14722

29444

44166

58888

73610

<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:

0.524

AC:

79759

AN:

152154

Hom.:

21881

Cov.:

AF XY:

0.524

AC XY:

38983

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.696

AC:

28884

AN:

41516

American (AMR)

AF:

0.374

AC:

5720

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

1595

AN:

3470

East Asian (EAS)

AF:

0.506

AC:

2614

AN:

5164

South Asian (SAS)

AF:

0.444

AC:

2141

AN:

4826

European-Finnish (FIN)

AF:

0.553

AC:

5865

AN:

10598

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31202

AN:

67982

Other (OTH)

AF:

0.512

AC:

1080

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1960

3919

5879

7838

9798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.466

Hom.:

13794

Bravo

AF:

0.517

Asia WGS

AF:

0.499

AC:

1733

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Val553Val in exon 10 of FAM20C: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 75.19% (994/1322) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs36170987). -

Oct 20, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lethal osteosclerotic bone dysplasia

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.1

(source)

DANN

Benign

0.55

PhyloP100

0.087

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over