ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- no assertion criteria provided
- Submissions:
- 1
- First in ClinVar:
- Aug 19, 2023
- Most recent Submission:
- Aug 19, 2023
- Last evaluated:
- Aug 14, 2023
- Accession:
- VCV002575312.1
- Variation ID:
- 2575312
- Description:
- 160bp deletion
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NM_031157.4(HNRNPA1):c.1064-63_*4+37del
- Allele ID
- 2740207
- Variant type
- Deletion
- Variant length
- 160 bp
- Cytogenetic location
- 12q13.13
- Genomic location
- 12: 54284194-54284353 (GRCh38) GRCh38 UCSC
- 12: 54677978-54678137 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_031157.4:c.1064-63_*4+37del MANE Select splice acceptor
splice donorNM_002136.4:c.908-63_*4+37del splice acceptor
splice donorNC_000012.12:g.54284195_54284354del NC_000012.11:g.54677979_54678138del NG_033830.1:g.8492_8651del - Protein change
- -
- Other names
- -
- Canonical SPDI
- -
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- OMIM: 164017.0004
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | no assertion criteria provided | Aug 14, 2023 | RCV003320502.1 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Aug 14, 2023)
|
no assertion criteria provided
Method: literature only
|
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV004024602.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
Comment on evidence:
In affected members of a large multigenerational Finnish family with distal myopathy-3 (MPD3; 610099) originally reported by Mahjneh et al. (2003), Hackman et al. (2021) … (more)
In affected members of a large multigenerational Finnish family with distal myopathy-3 (MPD3; 610099) originally reported by Mahjneh et al. (2003), Hackman et al. (2021) identified a heterozygous 160-bp deletion (chr12.54,677,979-54,678,138, NM_031157.4) affecting exon 10 of the HNRNPA1 gene, which encodes part of the PrLD domain. The deletion, which was found by a combination of linkage analysis, genome sequencing, and copy number variation analysis, was confirmed by Sanger sequencing and segregated with the disorder in the family. It was not present in the gnomAD database. A muscle sample from 1 of the patients showed an abnormal HNRNPA1 transcript that lacked exon 10. The observed splicing defect was predicted to result in a frameshift and premature termination (Gly356AsnfsTer4). The mutation was also predicted to encode a minor abnormal transcript leading to a longer C-terminal tail encoded by 3-prime UTR exons. Western blot analysis of skeletal muscle biopsy of 1 patient showed about 50% reduced expression of both HNRNPA1 isoforms. Muscle biopsies also showed small SQSTM1 (601530)- and larger TDP43 (605078)-labeled inclusions. Some biopsies showed increased HNRNPA1 sarcoplasmic labeling; 1 fiber in 1 biopsy showed moderate HNRNPA1 accumulation, but the authors noted that there was no strong focal cytoplasmic accumulation. (less)
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Dominant Distal Myopathy 3 (MPD3) Caused by a Deletion in the HNRNPA1 Gene. | Hackman P | Neurology. Genetics | 2021 | PMID: 34722876 |
| A distinct phenotype of distal myopathy in a large Finnish family. | Mahjneh I | Neurology | 2003 | PMID: 12847162 |
Record last updated Aug 19, 2023