7-193245-G-C

Variant names:

• chr7-193245-G-C
• rs150401144
• NM_020223.4:c.46G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020223.4(FAM20C):​c.46G>C​(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,316,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: FAM20C NM_020223.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• 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: G2P, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000240093 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20393977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.46G>C	p.Val16Leu	missense_variant	Exon 1 of 10	ENST00000313766.6	NP_064608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6	c.46G>C	p.Val16Leu	missense_variant	Exon 1 of 10	1	NM_020223.4	ENSP00000322323.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.60e-7 AC: 1 AN: 1316306 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 649846

African (AFR) AF: 0.00 AC: 0 AN: 26584

American (AMR) AF: 0.00 AC: 0 AN: 32230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22214

East Asian (EAS) AF: 0.00 AC: 0 AN: 29504

South Asian (SAS) AF: 0.00 AC: 0 AN: 76776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038098

Other (OTH) AF: 0.00 AC: 0 AN: 53318

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.26	T
PhyloP100		3.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.19
Sift	Benign	0.16	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.35		Loss of MoRF binding (P = 0.0982);
MVP		0.37
MPC		0.47
ClinPred		0.41	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.66
Mutation Taster		=89/11	polymorphism

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: rs150401144; hg19: chr7-193245;