NM_014171.6:c.7_8delTG
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_014171.6(CRIPT):c.7_8delTG(p.Cys3ArgfsTer4) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000713 in 1,402,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
CRIPT
NM_014171.6 frameshift
NM_014171.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.03
Publications
1 publications found
Genes affected
CRIPT (HGNC:14312): (CXXC repeat containing interactor of PDZ3 domain) This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]
PIGF (HGNC:8962): (phosphatidylinositol glycan anchor biosynthesis class F) This gene encodes a protein involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor, a glycolipid containing three mannose molecules in its core backbone, is found on many blood cells where it serves to anchor proteins to the cell surface. The encoded protein and another GPI synthesis protein, PIGO, function in the transfer of ethanolaminephosphate to the third mannose in GPI. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
PIGF Gene-Disease associations (from GenCC):
- onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndromeInheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-46617285-GGT-G is Pathogenic according to our data. Variant chr2-46617285-GGT-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1343340.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_014171.6. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CRIPT | NM_014171.6 | MANE Select | c.7_8delTG | p.Cys3ArgfsTer4 | frameshift | Exon 1 of 5 | NP_054890.1 | Q9P021 | |
| PIGF | NM_002643.4 | MANE Select | c.-339_-338delAC | upstream_gene | N/A | NP_002634.1 | Q6IB04 | ||
| PIGF | NM_173074.3 | c.-339_-338delAC | upstream_gene | N/A | NP_775097.1 | Q07326-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CRIPT | ENST00000238892.4 | TSL:1 MANE Select | c.7_8delTG | p.Cys3ArgfsTer4 | frameshift | Exon 1 of 5 | ENSP00000238892.3 | Q9P021 | |
| CRIPT | ENST00000923190.1 | c.7_8delTG | p.Cys3ArgfsTer4 | frameshift | Exon 2 of 6 | ENSP00000593249.1 | |||
| CRIPT | ENST00000718244.1 | n.7_8delTG | non_coding_transcript_exon | Exon 1 of 6 | ENSP00000520689.1 | A0ABB0MV94 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000630 AC: 1AN: 158696 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
158696
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: 7.13e-7 AC: 1AN: 1402964Hom.: 0 AF XY: 0.00000144 AC XY: 1AN XY: 692114 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1402964
Hom.:
AF XY:
AC XY:
1
AN XY:
692114
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32192
American (AMR)
AF:
AC:
0
AN:
35780
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25184
East Asian (EAS)
AF:
AC:
0
AN:
36768
South Asian (SAS)
AF:
AC:
0
AN:
79612
European-Finnish (FIN)
AF:
AC:
0
AN:
49170
Middle Eastern (MID)
AF:
AC:
0
AN:
5668
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1080432
Other (OTH)
AF:
AC:
0
AN:
58158
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
2
-
-
Rothmund-Thomson syndrome type 3 (2)
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
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