13-23203692-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
This summary comes from the ClinGen Evidence Repository: The NM_000231.3: c.1-3C>T variant is an intronic SGCG variant that is located in a splice region. The computational splicing predictor SpliceAI gives a score of 0.02 for acceptor loss, suggesting that the variant has no impact on splicing since it does not exceed the designated LGMD VCEP threshold (≤0.05) (BP4). The highest minor allele frequency of this variant is 0.0003793 (6/15820 exome chromosomes) in the African/African American population in gnomAD v2.1.1, which is greater than the ClinGen LGMD threshold (≤0.00009) for PM2_Supporting, and therefore does not meet this criterion (PM2_Supporting, BA1, BS1 criteria not met). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Limb-Girdle Muscular Dystrophy VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA6909546/MONDO:0015152/185
Frequency
Consequence
NM_000231.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000244 AC: 6AN: 245446Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132476
GnomAD4 exome AF: 0.00000480 AC: 7AN: 1457276Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724690
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2C Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 10, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 18, 2019 | - - |
Autosomal recessive limb-girdle muscular dystrophy Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen | Jan 08, 2025 | The NM_000231.3: c.1-3C>T variant is an intronic SGCG variant that is located in a splice region. The computational splicing predictor SpliceAI gives a score of 0.02 for acceptor loss, suggesting that the variant has no impact on splicing since it does not exceed the designated LGMD VCEP threshold (≤0.05) (BP4). The highest minor allele frequency of this variant is 0.0003793 (6/15820 exome chromosomes) in the African/African American population in gnomAD v2.1.1, which is greater than the ClinGen LGMD threshold (≤0.00009) for PM2_Supporting, and therefore does not meet this criterion (PM2_Supporting, BA1, BS1 criteria not met). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Limb-Girdle Muscular Dystrophy VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): BP4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at