Variant rs144007479 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_020223.4(FAM20C):c.1218T>A(p.Pro406=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,536,036 control chromosomes in the GnomAD database, including 730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 64 hom., cov: 33)

Exomes 𝑓: 0.028 ( 666 hom. )

Consequence

FAM20C
NM_020223.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.50

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 7-255994-T-A is Benign according to our data. Variant chr7-255994-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 504906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0262 (3989/152290) while in subpopulation NFE AF= 0.0315 (2142/68012). AF 95% confidence interval is 0.0304. There are 64 homozygotes in gnomad4. There are 1841 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20C	NM_020223.4 linkuse as main transcript	c.1218T>A	p.Pro406=	synonymous_variant	6/10	ENST00000313766.6	NP_064608.2
FAM20C	XR_007060117.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6 linkuse as main transcript	c.1218T>A	p.Pro406=	synonymous_variant	6/10	1	NM_020223.4	ENSP00000322323	P1	Q8IXL6-1
FAM20C	ENST00000515795.1 linkuse as main transcript	n.875T>A		non_coding_transcript_exon_variant	3/7	1

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3993

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0195

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0315

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0225

AC:

3159

AN:

140380

Hom.:

AF XY:

0.0218

AC XY:

1641

AN XY:

75352

show subpopulations

Gnomad AFR exome

AF:

0.0310

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00858

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0330

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0285

AC:

39386

AN:

1383746

Hom.:

666

Cov.:

AF XY:

0.0279

AC XY:

19059

AN XY:

682822

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.0345

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.00817

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.0316

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0262

AC:

3989

AN:

152290

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1841

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0284

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0195

Gnomad4 NFE

AF:

0.0315

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0297

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

p.Pro406Pro in exon 6 of FAM20C: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 3.57% (215/6028) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs144007479). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.0

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over