chr7-246502-G-GGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The ENST00000515795.1(FAM20C):n.510_511insGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAG variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,341,114 control chromosomes in the GnomAD database, including 72,792 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 6675 hom., cov: 40)

Exomes 𝑓: 0.27 ( 66117 hom. )

Consequence

FAM20C
ENST00000515795.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 8.67

Publications

1 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 -15 ACMG points.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

BP6

Variant 7-246502-G-GGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGC is Benign according to our data. Variant chr7-246502-G-GGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGC is described in ClinVar as [Benign]. Clinvar id is 402845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FAM20C	NM_020223.4 link	c.953_956+30dupACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG	intron_variant	Intron 4 of 9	ENST00000313766.6	NP_064608.2	Q8IXL6-1
FAM20C	XR_001744837.2 link	n.1503_1506+30dupACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG	intron_variant	Intron 3 of 5
FAM20C	XR_007060116.1 link	n.1582_1585+30dupACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG	intron_variant	Intron 4 of 6
FAM20C	XR_007060117.1 link	n.1503_1506+30dupACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000515795.1 link	n.510_511insGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAG		non_coding_transcript_exon_variant	Exon 1 of 7	1
FAM20C	ENST00000313766.6 link	c.864-11_864-10insGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAG		intron_variant	Intron 3 of 9	1	NM_020223.4	ENSP00000322323.5		Q8IXL6-1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

43540

AN:

109688

Hom.:

6672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.489

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.273

AC:

335863

AN:

1231342

Hom.:

66117

Cov.:

AF XY:

0.274

AC XY:

167017

AN XY:

610540

show subpopulations

African (AFR)

AF:

0.244

AC:

6281

AN:

25772

American (AMR)

AF:

0.204

AC:

6908

AN:

33926

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

6166

AN:

22966

East Asian (EAS)

AF:

0.366

AC:

12536

AN:

34210

South Asian (SAS)

AF:

0.236

AC:

17213

AN:

73002

European-Finnish (FIN)

AF:

0.270

AC:

9079

AN:

33608

Middle Eastern (MID)

AF:

0.308

AC:

1608

AN:

5220

European-Non Finnish (NFE)

AF:

0.275

AC:

260963

AN:

950300

Other (OTH)

AF:

0.289

AC:

15109

AN:

52338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

8463

16925

25388

33850

42313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.397

AC:

43564

AN:

109772

Hom.:

6675

Cov.:

AF XY:

0.393

AC XY:

21057

AN XY:

53590

show subpopulations

African (AFR)

AF:

0.468

AC:

10725

AN:

22932

American (AMR)

AF:

0.327

AC:

4087

AN:

12512

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1010

AN:

2666

East Asian (EAS)

AF:

0.447

AC:

1927

AN:

4314

South Asian (SAS)

AF:

0.317

AC:

1101

AN:

3474

European-Finnish (FIN)

AF:

0.349

AC:

2803

AN:

8030

Middle Eastern (MID)

AF:

0.483

AC:

117

AN:

242

European-Non Finnish (NFE)

AF:

0.391

AC:

20828

AN:

53330

Other (OTH)

AF:

0.395

AC:

620

AN:

1568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1246

2492

3738

4984

6230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.204

Hom.:

843

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

FAM20C-related disorder

Benign:1

Mar 03, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Lethal osteosclerotic bone dysplasia

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.7

Mutation Taster

=14/186

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr7-246502-G-GGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGC

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