NM_001492.6:c.1090_1092delATG
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_001492.6(GDF1):c.1090_1092delATG(p.Met364del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000000705 in 1,419,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
GDF1
NM_001492.6 conservative_inframe_deletion
NM_001492.6 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.14
Publications
1 publications found
Genes affected
GDF1 (HGNC:4214): (growth differentiation factor 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]
CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]
CERS1 Gene-Disease associations (from GenCC):
- progressive myoclonic epilepsy type 8Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001492.6. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 19-18868623-CCAT-C is Pathogenic according to our data. Variant chr19-18868623-CCAT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 522570.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GDF1 | NM_001492.6 | c.1090_1092delATG | p.Met364del | conservative_inframe_deletion | Exon 8 of 8 | ENST00000247005.8 | NP_001483.3 | |
| CERS1 | NM_021267.5 | c.*1359_*1361delATG | 3_prime_UTR_variant | Exon 8 of 8 | ENST00000623882.4 | NP_067090.1 | ||
| GDF1 | NM_001387438.1 | c.1090_1092delATG | p.Met364del | conservative_inframe_deletion | Exon 5 of 5 | NP_001374367.1 | ||
| CERS1 | NM_001387440.1 | c.*1951_*1953delATG | 3_prime_UTR_variant | Exon 7 of 7 | NP_001374369.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GDF1 | ENST00000247005.8 | c.1090_1092delATG | p.Met364del | conservative_inframe_deletion | Exon 8 of 8 | 1 | NM_001492.6 | ENSP00000247005.5 | ||
| CERS1 | ENST00000623882.4 | c.*1359_*1361delATG | 3_prime_UTR_variant | Exon 8 of 8 | 1 | NM_021267.5 | ENSP00000485308.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00 AC: 0AN: 182372 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
182372
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 7.05e-7 AC: 1AN: 1419180Hom.: 0 AF XY: 0.00000142 AC XY: 1AN XY: 701970 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1419180
Hom.:
AF XY:
AC XY:
1
AN XY:
701970
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32574
American (AMR)
AF:
AC:
0
AN:
38960
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25304
East Asian (EAS)
AF:
AC:
0
AN:
37476
South Asian (SAS)
AF:
AC:
0
AN:
80738
European-Finnish (FIN)
AF:
AC:
0
AN:
49152
Middle Eastern (MID)
AF:
AC:
0
AN:
5714
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1090560
Other (OTH)
AF:
AC:
1
AN:
58702
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Right atrial isomerism Pathogenic:1
Apr 18, 2018
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.