rs372152495
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1
The NM_000337.6(SGCD):āc.144G>Cā(p.Val48=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000172 in 1,611,860 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00093 ( 0 hom., cov: 32)
Exomes š: 0.000093 ( 0 hom. )
Consequence
SGCD
NM_000337.6 synonymous
NM_000337.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.08
Genes affected
SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 5-156344629-G-C is Benign according to our data. Variant chr5-156344629-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 139099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000933 (142/152210) while in subpopulation AFR AF= 0.00328 (136/41516). AF 95% confidence interval is 0.00283. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCD | NM_000337.6 | c.144G>C | p.Val48= | synonymous_variant | 3/9 | ENST00000337851.9 | |
LOC124901120 | XR_007059016.1 | n.234+2824C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.144G>C | p.Val48= | synonymous_variant | 3/9 | 1 | NM_000337.6 | P4 | |
SGCD | ENST00000435422.7 | c.141G>C | p.Val47= | synonymous_variant | 2/8 | 1 | A1 | ||
SGCD | ENST00000517913.5 | c.144G>C | p.Val48= | synonymous_variant | 5/10 | 5 | |||
SGCD | ENST00000524347.2 | c.144G>C | p.Val48= | synonymous_variant, NMD_transcript_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000934 AC: 142AN: 152092Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000182 AC: 45AN: 246876Hom.: 0 AF XY: 0.000149 AC XY: 20AN XY: 133974
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GnomAD4 exome AF: 0.0000932 AC: 136AN: 1459650Hom.: 0 Cov.: 32 AF XY: 0.0000882 AC XY: 64AN XY: 726034
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GnomAD4 genome ? AF: 0.000933 AC: 142AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000994 AC XY: 74AN XY: 74428
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 21, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2012 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 21, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 15, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
SGCD-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 17, 2015 | - - |
Dilated cardiomyopathy 1L Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at