rs796051854
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_020223.4(FAM20C):c.956+5G>C variant causes a splice donor 5th base, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 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_donor_5th_base, intron
NM_020223.4 splice_donor_5th_base, intron
Scores
2
Splicing: ADA: 0.9647
2
Clinical Significance
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.
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 | UniProt |
---|---|---|---|---|---|---|---|
FAM20C | NM_020223.4 | c.956+5G>C | splice_donor_5th_base_variant, intron_variant | ENST00000313766.6 | |||
FAM20C | XR_001744837.2 | n.1506+5G>C | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | ||||
FAM20C | XR_007060116.1 | n.1585+5G>C | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | ||||
FAM20C | XR_007060117.1 | n.1506+5G>C | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM20C | ENST00000313766.6 | c.956+5G>C | splice_donor_5th_base_variant, intron_variant | 1 | NM_020223.4 | P1 | |||
FAM20C | ENST00000515795.1 | n.613+5G>C | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 40
GnomAD3 genomes
?
Cov.:
40
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 40
GnomAD4 genome
?
Cov.:
40
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Lethal osteosclerotic bone dysplasia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 48
DS_DL_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at