7-193230-G-C

Variant names:

• chr7-193230-G-C
• rs1367064980
• NM_020223.4:c.31G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020223.4(FAM20C):​c.31G>C​(p.Val11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,464,468 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: 𝑓 0.0000067 (0 hom., cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: FAM20C NM_020223.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38200146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.31G>C	p.Val11Leu	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.31G>C	p.Val11Leu	missense_variant	Exon 1 of 10	1	NM_020223.4	ENSP00000322323.5
ENSG00000240093	ENST00000467050.1	n.233+718C>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 149834 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: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1314634 Hom.: 0 Cov.: 30 AF XY: 0.00000154 AC XY: 1 AN XY: 649296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000338

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149834 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73088

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.22	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.012	D
Sift4G	Benign	0.31	T
Polyphen		0.59	P
Vest4		0.23
MutPred		0.63		Loss of catalytic residue at V11 (P = 0.0419);
MVP		0.73
MPC		1.2
ClinPred		0.84	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.25
gMVP		0.63

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: rs1367064980; hg19: chr7-193230;