7-193222-G-C

Variant names:

• chr7-193222-G-C
• NM_020223.4:c.23G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020223.4(FAM20C):​c.23G>C​(p.Arg8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 149,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8Q) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 33)
• Consequence: FAM20C NM_020223.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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]

ENSG00000240093 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.23G>C	p.Arg8Pro	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.23G>C	p.Arg8Pro	missense_variant	Exon 1 of 10	1	NM_020223.4	ENSP00000322323.5
ENSG00000240093	ENST00000467050.1	n.233+726C>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149776 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149882 Hom.: 0 Cov.: 33 AF XY: 0.0000137 AC XY: 1 AN XY: 73166

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T
Eigen	Benign	0.096
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.39	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.79	P
Vest4		0.43
MutPred		0.65		Gain of sheet (P = 0.0043);
MVP		0.69
MPC		1.3
ClinPred		0.94	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.62
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-193222;