NM_015426.5:c.1048delC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015426.5(POC1A):c.1048delC(p.Gln350ArgfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
POC1A
NM_015426.5 frameshift
NM_015426.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.38
Publications
1 publications found
Genes affected
POC1A (HGNC:24488): (POC1 centriolar protein A) POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutations in this gene result in short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome. [provided by RefSeq, Sep 2012]
POC1A Gene-Disease associations (from GenCC):
- short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-52096645-TG-T is Pathogenic according to our data. Variant chr3-52096645-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 981226.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_015426.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| POC1A | MANE Select | c.1048delC | p.Gln350ArgfsTer4 | frameshift | Exon 10 of 11 | NP_056241.3 | |||
| POC1A | c.934delC | p.Gln312ArgfsTer4 | frameshift | Exon 10 of 11 | NP_001155053.1 | Q8NBT0-3 | |||
| POC1A | c.982-20661delC | intron | N/A | NP_001155052.1 | Q8NBT0-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| POC1A | TSL:1 MANE Select | c.1048delC | p.Gln350ArgfsTer4 | frameshift | Exon 10 of 11 | ENSP00000296484.2 | Q8NBT0-1 | ||
| POC1A | TSL:1 | c.982-20661delC | intron | N/A | ENSP00000378421.2 | Q8NBT0-2 | |||
| POC1A | c.1012delC | p.Gln338ArgfsTer4 | frameshift | Exon 10 of 11 | ENSP00000609814.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 249820 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
249820
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460866Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726786 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1460866
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
726786
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33354
American (AMR)
AF:
AC:
0
AN:
44640
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26110
East Asian (EAS)
AF:
AC:
0
AN:
39570
South Asian (SAS)
AF:
AC:
0
AN:
86210
European-Finnish (FIN)
AF:
AC:
0
AN:
53274
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111596
Other (OTH)
AF:
AC:
0
AN:
60352
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
POC1A-related syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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