Genetic Variant FAM20C:p.Arg8Arg (chr7-193223-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_020223.4(FAM20C):c.24G>C(p.Arg8Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000082 in 1,463,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

FAM20C
NM_020223.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.822

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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 7-193223-G-C is Benign according to our data. Variant chr7-193223-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2968405.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.822 with no splicing effect.

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.24G>C	p.Arg8Arg	synonymous	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.24G>C	p.Arg8Arg	synonymous	Exon 1 of 10	ENSP00000322323.5	Q8IXL6-1
FAM20C	ENST00000942064.1		c.24G>C	p.Arg8Arg	synonymous	Exon 1 of 11	ENSP00000612123.1
FAM20C	ENST00000866115.1		c.24G>C	p.Arg8Arg	synonymous	Exon 1 of 11	ENSP00000536174.1

Frequencies

GnomAD3 genomes

AF:

0.0000400

AC:

AN:

149836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

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:

0.00

AC:

AN:

118796

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1313404

Hom.:

Cov.:

AF XY:

0.00000308

AC XY:

AN XY:

648684

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

26690

American (AMR)

AF:

0.00

AC:

AN:

32508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22026

East Asian (EAS)

AF:

0.00

AC:

AN:

29530

South Asian (SAS)

AF:

0.00

AC:

AN:

77066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035532

Other (OTH)

AF:

0.0000189

AC:

AN:

52904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000400

AC:

AN:

149836

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

73074

show subpopulations

African (AFR)

AF:

0.000146

AC:

AN:

41196

American (AMR)

AF:

0.00

AC:

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67172

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Likely benign

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

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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