rs749205073
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_000023.4(SGCA):c.270C>T(p.Tyr90Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
SGCA
NM_000023.4 synonymous
NM_000023.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.50
Genes affected
SGCA (HGNC:10805): (sarcoglycan alpha) This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 17-50167694-C-T is Benign according to our data. Variant chr17-50167694-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 289891.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.
BP7
Synonymous conserved (PhyloP=-2.5 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SGCA | NM_000023.4 | c.270C>T | p.Tyr90Tyr | synonymous_variant | 3/10 | ENST00000262018.8 | NP_000014.1 | |
| SGCA | NM_001135697.3 | c.270C>T | p.Tyr90Tyr | synonymous_variant | 3/8 | NP_001129169.1 | ||
| SGCA | NR_135553.2 | n.306C>T | non_coding_transcript_exon_variant | 3/9 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SGCA | ENST00000262018.8 | c.270C>T | p.Tyr90Tyr | synonymous_variant | 3/10 | 1 | NM_000023.4 | ENSP00000262018.3 |
Frequencies
GnomAD3 genomes 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249038Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134808
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GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461216Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 726856
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GnomAD4 genome 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74348
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2018 | The c.270 C>T variant in the SGCA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.270 C>T variant is observed in 6/25644 (0.02%) alleles from individuals of Finnish European background in large population cohorts, and no individuals were reported to be homozygous (Lek et al., 2016). The c.270 C>T variant represents a synonymous amino acid substitution that occurs at a position that is not conserved across species. In silico prediction models predict that c.270 C>T may enhance a cryptic splice acceptor site in exon 3, and may cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. We interpret c.270 C>T as a variant of uncertain significance. - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 16, 2016 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | SGCA: BP4, BP7 - |
Autosomal recessive limb-girdle muscular dystrophy type 2D Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 25, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at