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GeneBe

7-246502-G-GGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 10P and 4B. PVS1PM2BS1

The NM_020223.4(FAM20C):c.956+30_956+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG variant causes a stop gained, frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000589 in 1,358,200 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L317L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., cov: 40)
Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

FAM20C
NM_020223.4 stop_gained, frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.67
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000453 (5/110480) while in subpopulation EAS AF= 0.000923 (4/4334). AF 95% confidence interval is 0.000315. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 40. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAM20CNM_020223.4 linkuse as main transcriptc.956+30_956+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG stop_gained, frameshift_variant 4/10 ENST00000313766.6
FAM20CXR_001744837.2 linkuse as main transcriptn.1506+30_1506+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG non_coding_transcript_exon_variant 3/6
FAM20CXR_007060116.1 linkuse as main transcriptn.1585+30_1585+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG non_coding_transcript_exon_variant 4/7
FAM20CXR_007060117.1 linkuse as main transcriptn.1506+30_1506+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG non_coding_transcript_exon_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAM20CENST00000313766.6 linkuse as main transcriptc.956+30_956+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG stop_gained, frameshift_variant 4/101 NM_020223.4 P1Q8IXL6-1
FAM20CENST00000515795.1 linkuse as main transcriptn.613+30_613+31insACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCGACAGGTGAGCCCTTCCTTCCTCCCTCCATCCGCG non_coding_transcript_exon_variant 1/71

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000453
AC:
5
AN:
110392
Hom.:
0
Cov.:
40
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000921
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000187
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000240
AC:
3
AN:
1247720
Hom.:
0
Cov.:
34
AF XY:
0.00000323
AC XY:
2
AN XY:
618324
show subpopulations
Gnomad4 AFR exome
AF:
0.0000386
Gnomad4 AMR exome
AF:
0.0000294
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000291
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000453
AC:
5
AN:
110480
Hom.:
0
Cov.:
40
AF XY:
0.0000371
AC XY:
2
AN XY:
53962
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000923
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000187
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771282640; hg19: chr7-286468; API