rs796051854

Positions:

• chr7-246512-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_020223.4(FAM20C):​c.956+5G>C variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 40)
• Consequence: FAM20C NM_020223.4 splice_region, intron
• Scores: Splicing: ADA: 0.9647
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.54

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-246512-G-C is Pathogenic according to our data. Variant chr7-246512-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1029.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-246512-G-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.956+5G>C		splice_region_variant, intron_variant		ENST00000313766.6	NP_064608.2
FAM20C	XR_001744837.2	n.1506+5G>C		splice_region_variant, intron_variant
FAM20C	XR_007060116.1	n.1585+5G>C		splice_region_variant, intron_variant
FAM20C	XR_007060117.1	n.1506+5G>C		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6	c.956+5G>C		splice_region_variant, intron_variant		1	NM_020223.4	ENSP00000322323.5
FAM20C	ENST00000515795.1	n.613+5G>C		splice_region_variant, intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 40

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 40

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lethal osteosclerotic bone dysplasia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.96
dbscSNV1_RF	Pathogenic	0.76
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.51		Position offset: 48
DS_DL_spliceai		0.44		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs796051854; hg19: chr7-286478;