chr12-50108041-GAA-G
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005276.4(GPD1):c.866_867delAA(p.Lys289ArgfsTer48) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000685 in 1,458,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
GPD1
NM_005276.4 frameshift
NM_005276.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.32
Publications
0 publications found
Genes affected
GPD1 (HGNC:4455): (glycerol-3-phosphate dehydrogenase 1) This gene encodes a member of the NAD-dependent glycerol-3-phosphate dehydrogenase family. The encoded protein plays a critical role in carbohydrate and lipid metabolism by catalyzing the reversible conversion of dihydroxyacetone phosphate (DHAP) and reduced nicotine adenine dinucleotide (NADH) to glycerol-3-phosphate (G3P) and NAD+. The encoded cytosolic protein and mitochondrial glycerol-3-phosphate dehydrogenase also form a glycerol phosphate shuttle that facilitates the transfer of reducing equivalents from the cytosol to mitochondria. Mutations in this gene are a cause of transient infantile hypertriglyceridemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
GPD1 Gene-Disease associations (from GenCC):
- transient infantile hypertriglyceridemia and hepatosteatosisInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 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 12-50108041-GAA-G is Pathogenic according to our data. Variant chr12-50108041-GAA-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 521341.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005276.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GPD1 | NM_005276.4 | MANE Select | c.866_867delAA | p.Lys289ArgfsTer48 | frameshift | Exon 7 of 8 | NP_005267.2 | ||
| GPD1 | NM_001257199.2 | c.797_798delAA | p.Lys266ArgfsTer48 | frameshift | Exon 7 of 8 | NP_001244128.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GPD1 | ENST00000301149.8 | TSL:1 MANE Select | c.866_867delAA | p.Lys289ArgfsTer48 | frameshift | Exon 7 of 8 | ENSP00000301149.3 | ||
| GPD1 | ENST00000548814.1 | TSL:2 | c.797_798delAA | p.Lys266ArgfsTer48 | frameshift | Exon 7 of 8 | ENSP00000446768.1 | ||
| GPD1 | ENST00000547190.5 | TSL:5 | n.675_676delAA | non_coding_transcript_exon | Exon 6 of 6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000241 AC: 6AN: 249070 AF XY: 0.0000297 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
249070
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1458890Hom.: 0 AF XY: 0.00000689 AC XY: 5AN XY: 725848 show subpopulations
GnomAD4 exome
AF:
AC:
10
AN:
1458890
Hom.:
AF XY:
AC XY:
5
AN XY:
725848
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33414
American (AMR)
AF:
AC:
0
AN:
44640
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26066
East Asian (EAS)
AF:
AC:
0
AN:
39686
South Asian (SAS)
AF:
AC:
0
AN:
86010
European-Finnish (FIN)
AF:
AC:
1
AN:
53376
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1109698
Other (OTH)
AF:
AC:
0
AN:
60270
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
1
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4
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0.40
0.60
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0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Dec 06, 2016
Ambry Genetics
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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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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