NG_033784.1(NM_001101677.1):c.346-1G>A in the SOHLH1 gene has an allele frequency of 0.015 in European (Finnish) subpopulation in the gnomAD database. 5 homozygous occurrences are observed in the gnomAD database. This variant destroys the canonical splice donor site. It is was predicted to lead to skipping of exon 4 or activation of a cryptic splice acceptor site in exon 4. The c.346-1G>A has been detected in two individuals with non-obstructive azoospermia (PMID: 20506135, 28718531). In the patient reported by Nakamura (PMID: 20506135), c.346-1G>A mutation was not detected in both parents of each probands, indicating a de novo event. We interpret it as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PVS1, PS2, PP4, BS1.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Benign
- Review status:
- criteria provided, single submitter
- Submissions:
- 3
- First in ClinVar:
- Sep 15, 2018
- Most recent Submission:
- May 4, 2020
- Last evaluated:
- Dec 31, 2019
- Accession:
- VCV000560884.6
- Variation ID:
- 560884
- Description:
- single nucleotide variant
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NM_001101677.2(SOHLH1):c.346-1G>A
- Allele ID
- 551991
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 9q34.3
- Genomic location
- 9: 135697628 (GRCh38) GRCh38 UCSC
- 9: 138589474 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001101677.2:c.346-1G>A MANE Select splice acceptor NM_001012415.3:c.346-1G>A splice acceptor NC_000009.12:g.135697628C>T NC_000009.11:g.138589474C>T NG_033070.1:g.444C>T NG_033070.2:g.444C>T NG_033784.1:g.6901G>A NG_033784.2:g.9484G>A - Protein change
- -
- Other names
- IVS3AS, G-A, -1 (rs140132974)
- Canonical SPDI
- NC_000009.12:135697627:C:T
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- 0.00300 (T)
- Allele frequency
- NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
- Trans-Omics for Precision Medicine (TOPMed) 0.00107
- 1000 Genomes Project 0.00300
- The Genome Aggregation Database (gnomAD) 0.00306
- The Genome Aggregation Database (gnomAD) 0.00173
- Trans-Omics for Precision Medicine (TOPMed) 0.00068
- The Genome Aggregation Database (gnomAD), exomes 0.00290
- Exome Aggregation Consortium (ExAC) 0.00329
- Links
- dbSNP: rs140132974
- OMIM: 610224.0003
- 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 | Jan 6, 2020 | RCV000991169.1 | |
| Pathogenic | 1 | no assertion criteria provided | Sep 11, 2018 | RCV000679811.1 | |
| Benign | 1 | criteria provided, single submitter | Dec 31, 2019 | RCV000899225.4 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Benign
(Dec 31, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001043479.2
First in ClinVar: Dec 17, 2019 Last updated: May 04, 2020 |
|
|
|
Pathogenic
(Sep 11, 2018)
|
no assertion criteria provided
Method: literature only
|
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000807191.1
First in ClinVar: Sep 15, 2018 Last updated: Sep 15, 2018 |
Comment on evidence:
In 2 unrelated Korean men with nonobstructive azoospermia (SPGF32; 618115), Choi et al. (2010) identified heterozygosity for a de novo splice site mutation (c.346-1G-A, NM_001012415.1) … (more)
In 2 unrelated Korean men with nonobstructive azoospermia (SPGF32; 618115), Choi et al. (2010) identified heterozygosity for a de novo splice site mutation (c.346-1G-A, NM_001012415.1) in intron 3 of the SOHLH1 gene that was not found in their parents or in 159 Korean men with a normal sperm count. RT-PCR analysis of mRNA from transiently transfected HEK293T cells revealed mutant transcripts that were shorter than wildtype, and sequence analysis confirmed an in-frame deletion (18 bp) within exon 4, resulting in truncation of the bHLH domain. In transcriptional activity assays, the mutant protein showed less than half of the activity of wildtype protein. Nakamura et al. (2017) analyzed 25 azoospermia-associated genes in 40 Japanese men with infertility due to nonobstructive azoospermia and identified the previously reported SOHLH1 c.346-1G-A splice site mutation in 2 patients. (less)
|
|
|
Pathogenic
(Jan 06, 2020)
|
no assertion criteria provided
Method: curation
|
Affected status: unknown
Allele origin:
germline
|
Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142406.1
First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
Comment:
NG_033784.1(NM_001101677.1):c.346-1G>A in the SOHLH1 gene has an allele frequency of 0.015 in European (Finnish) subpopulation in the gnomAD database. 5 homozygous occurrences are observed in … (more)
NG_033784.1(NM_001101677.1):c.346-1G>A in the SOHLH1 gene has an allele frequency of 0.015 in European (Finnish) subpopulation in the gnomAD database. 5 homozygous occurrences are observed in the gnomAD database. This variant destroys the canonical splice donor site. It is was predicted to lead to skipping of exon 4 or activation of a cryptic splice acceptor site in exon 4. The c.346-1G>A has been detected in two individuals with non-obstructive azoospermia (PMID: 20506135, 28718531). In the patient reported by Nakamura (PMID: 20506135), c.346-1G>A mutation was not detected in both parents of each probands, indicating a de novo event. We interpret it as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PVS1, PS2, PP4, BS1. (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 |
|---|---|---|---|---|
| Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations. | Nakamura S | Andrology | 2017 | PMID: 28718531 |
| Mutations in SOHLH1 gene associate with nonobstructive azoospermia. | Choi Y | Human mutation | 2010 | PMID: 20506135 |
Text-mined citations for rs140132974...
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Record last updated Jun 10, 2023