rs397514486
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001366722.1(GRIP1):c.1337_1340delAAGA(p.Lys446ThrfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 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: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GRIP1
NM_001366722.1 frameshift
NM_001366722.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.02
Publications
1 publications found
Genes affected
GRIP1 (HGNC:18708): (glutamate receptor interacting protein 1) This gene encodes a member of the glutamate receptor interacting protein family. The encoded scaffold protein binds to and mediates the trafficking and membrane organization of a number of transmembrane proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]
GRIP1 Gene-Disease associations (from GenCC):
- Fraser syndrome 3Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
- Fraser syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
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 12-66455422-GTCTT-G is Pathogenic according to our data. Variant chr12-66455422-GTCTT-G is described in ClinVar as [Pathogenic]. Clinvar id is 36971.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GRIP1 | NM_001366722.1 | c.1337_1340delAAGA | p.Lys446ThrfsTer8 | frameshift_variant | Exon 11 of 25 | ENST00000359742.9 | NP_001353651.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461836Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727226 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461836
Hom.:
AF XY:
AC XY:
1
AN XY:
727226
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111962
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
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
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8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Fraser syndrome 3 Pathogenic:1
May 01, 2012
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
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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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