5-156327232-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000337.6(SGCD):c.-44G>T variant causes a splice region change. The variant allele was found at a frequency of 0.0000263 in 152,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SGCD
NM_000337.6 splice_region
NM_000337.6 splice_region
Scores
2
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 6.63
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 4: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai [when BayesDel_noAF, Dann was below the threshold]
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SGCD | NM_000337.6 | c.-44G>T | splice_region_variant | 1/9 | ENST00000337851.9 | NP_000328.2 | ||
SGCD | NM_000337.6 | c.-44G>T | 5_prime_UTR_variant | 1/9 | ENST00000337851.9 | NP_000328.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.-44G>T | splice_region_variant | 1/9 | 1 | NM_000337.6 | ENSP00000338343.4 | |||
SGCD | ENST00000337851 | c.-44G>T | 5_prime_UTR_variant | 1/9 | 1 | NM_000337.6 | ENSP00000338343.4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152260Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 76Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 56
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74394
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 16, 2017 | - - |
not specified Other:1
not provided, no classification provided | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 09, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 5
DS_DL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at