Variant rs36170987 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020223.4(FAM20C):c.1659G>T(p.Val553=) 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

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 -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 id is 193730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-259884-G-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
FAM20C	NM_020223.4 linkuse as main transcript	c.1659G>T	p.Val553=	synonymous_variant	10/10	ENST00000313766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM20C	ENST00000313766.6 linkuse as main transcript	c.1659G>T	p.Val553=	synonymous_variant	10/10	1	NM_020223.4	P1	Q8IXL6-1
FAM20C	ENST00000515795.1 linkuse as main transcript	n.1316G>T		non_coding_transcript_exon_variant	7/7	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

GnomAD3 exomes

AF:

0.438

AC:

61566

AN:

140424

Hom.:

14510

AF XY:

0.439

AC XY:

33110

AN XY:

75414

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 SAS exome

AF:

0.438

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

Gnomad4 AFR exome

AF:

0.701

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.437

Gnomad4 FIN exome

AF:

0.526

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.524

AC:

79759

AN:

152154

Hom.:

21881

Cov.:

AF XY:

0.524

AC XY:

38983

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.696

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.460

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.444

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.512

Alfa

AF:

0.470

Hom.:

9605

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	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). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 20, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Lethal osteosclerotic bone dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.1

DANN

Benign

0.55

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

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