rs372152495

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1

The NM_000337.6(SGCD):ā€‹c.144G>Cā€‹(p.Val48Val) 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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 5.08
Variant links:
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 rank MANE Protein UniProt
SGCDNM_000337.6 linkc.144G>C p.Val48Val synonymous_variant Exon 3 of 9 ENST00000337851.9 NP_000328.2 Q92629-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SGCDENST00000337851.9 linkc.144G>C p.Val48Val synonymous_variant Exon 3 of 9 1 NM_000337.6 ENSP00000338343.4 Q92629-2
SGCDENST00000435422.7 linkc.141G>C p.Val47Val synonymous_variant Exon 2 of 8 1 ENSP00000403003.2 Q92629-1
SGCDENST00000517913.5 linkc.144G>C p.Val48Val synonymous_variant Exon 5 of 10 5 ENSP00000429378.1 Q92629-3
SGCDENST00000524347.2 linkn.144G>C non_coding_transcript_exon_variant Exon 3 of 6 5 ENSP00000430794.1 E5RI34

Frequencies

GnomAD3 genomes
AF:
0.000934
AC:
142
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00329
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000182
AC:
45
AN:
246876
Hom.:
0
AF XY:
0.000149
AC XY:
20
AN XY:
133974
show subpopulations
Gnomad AFR exome
AF:
0.00287
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000932
AC:
136
AN:
1459650
Hom.:
0
Cov.:
32
AF XY:
0.0000882
AC XY:
64
AN XY:
726034
show subpopulations
Gnomad4 AFR exome
AF:
0.00369
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000933
AC:
142
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.000994
AC XY:
74
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.00328
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00132
Hom.:
0
Bravo
AF:
0.00116
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 21, 2016- -
Benign, criteria provided, single submitterclinical testingGeneDxApr 08, 2014This 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 submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpApr 15, 2021- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsAug 21, 2020- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineApr 04, 2012proposed classification - variant undergoing re-assessment, contact laboratory -
Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:2
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 03, 2025- -
SGCD-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 02, 2020This 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 submitterclinical testingAmbry GeneticsMay 17, 2022This 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 submitterclinical testingCHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern OntarioSep 17, 2015- -
Dilated cardiomyopathy 1L Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
8.4
DANN
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372152495; hg19: chr5-155771639; API