rs36170987

Variant names:

• chr7-259884-G-T
• rs36170987
• NM_020223.4:c.1659G>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0870

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]

ACMG classification

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 rank	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.1659G>T	p.Val553Val	synonymous_variant	Exon 10 of 10	ENST00000313766.6	NP_064608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6	c.1659G>T	p.Val553Val	synonymous_variant	Exon 10 of 10	1	NM_020223.4	ENSP00000322323.5
FAM20C	ENST00000515795.1	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.: 35

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

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.: 74 AF XY: 0.452 AC XY: 308680 AN XY: 682612

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.: 35 AF XY: 0.524 AC XY: 38983 AN XY: 74362

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

Submissions by phenotype

not specified Benign:2

Oct 20, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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). -

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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
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

Other links and lift over

dbSNP: rs36170987; hg19: chr7-299850; COSMIC: COSV58237859; COSMIC: COSV58237859;