7-193451-C-T

Variant names:

• chr7-193451-C-T
• rs190382829
• NM_020223.4:c.252C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020223.4(FAM20C):​c.252C>T​(p.Asn84Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000061 in 1,310,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: FAM20C NM_020223.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 0 publications found

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: Genomics England PanelApp, Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000240093 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.564 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.252C>T	p.Asn84Asn	synonymous	Exon 1 of 10	NP_064608.2	Q8IXL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20C	ENST00000313766.6	TSL:1 MANE Select	c.252C>T	p.Asn84Asn	synonymous	Exon 1 of 10	ENSP00000322323.5	Q8IXL6-1
	FAM20C	ENST00000942064.1		c.252C>T	p.Asn84Asn	synonymous	Exon 1 of 11	ENSP00000612123.1
	FAM20C	ENST00000866115.1		c.252C>T	p.Asn84Asn	synonymous	Exon 1 of 11	ENSP00000536174.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000610 AC: 8 AN: 1310570 Hom.: 0 Cov.: 31 AF XY: 0.00000310 AC XY: 2 AN XY: 646162

African (AFR) AF: 0.00 AC: 0 AN: 26300

American (AMR) AF: 0.0000356 AC: 1 AN: 28062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22148

East Asian (EAS) AF: 0.00 AC: 0 AN: 27082

South Asian (SAS) AF: 0.00 AC: 0 AN: 71192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4934

European-Non Finnish (NFE) AF: 0.00000581 AC: 6 AN: 1031898

Other (OTH) AF: 0.0000189 AC: 1 AN: 52996

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

dbSNP: rs190382829; hg19: chr7-193451;