rs10071079

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000337.6(SGCD):​c.507G>A​(p.Ala169Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,580,166 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 11 hom., cov: 33)
Exomes 𝑓: 0.00067 ( 10 hom. )

Consequence

SGCD
NM_000337.6 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.663
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 5-156647468-G-A is Benign according to our data. Variant chr5-156647468-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 48120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.663 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (956/152218) while in subpopulation AFR AF= 0.0217 (902/41550). AF 95% confidence interval is 0.0205. There are 11 homozygotes in gnomad4. There are 440 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SGCDNM_000337.6 linkc.507G>A p.Ala169Ala synonymous_variant Exon 7 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.507G>A p.Ala169Ala synonymous_variant Exon 7 of 9 1 NM_000337.6 ENSP00000338343.4 Q92629-2
SGCDENST00000435422.7 linkc.504G>A p.Ala168Ala synonymous_variant Exon 6 of 8 1 ENSP00000403003.2 Q92629-1
SGCDENST00000517913.5 linkc.507G>A p.Ala169Ala synonymous_variant Exon 9 of 10 5 ENSP00000429378.1 Q92629-3

Frequencies

GnomAD3 genomes
AF:
0.00628
AC:
955
AN:
152100
Hom.:
11
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00139
AC:
284
AN:
204028
Hom.:
3
AF XY:
0.00117
AC XY:
128
AN XY:
108992
show subpopulations
Gnomad AFR exome
AF:
0.0203
Gnomad AMR exome
AF:
0.000773
Gnomad ASJ exome
AF:
0.000109
Gnomad EAS exome
AF:
0.0000661
Gnomad SAS exome
AF:
0.0000389
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000137
Gnomad OTH exome
AF:
0.000191
GnomAD4 exome
AF:
0.000672
AC:
960
AN:
1427948
Hom.:
10
Cov.:
29
AF XY:
0.000574
AC XY:
406
AN XY:
707038
show subpopulations
Gnomad4 AFR exome
AF:
0.0217
Gnomad4 AMR exome
AF:
0.000965
Gnomad4 ASJ exome
AF:
0.0000785
Gnomad4 EAS exome
AF:
0.0000259
Gnomad4 SAS exome
AF:
0.000147
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000101
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
AF:
0.00628
AC:
956
AN:
152218
Hom.:
11
Cov.:
33
AF XY:
0.00591
AC XY:
440
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.0217
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00179
Hom.:
3
Bravo
AF:
0.00687
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Aug 24, 2019
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 03, 2012
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

1.5% (59/3856) of Afr Amer chrom from ESP -

Aug 01, 2024
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:3
Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Aug 16, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:2
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 08, 2023
Genome-Nilou Lab
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

SGCD-related disorder Benign:1
May 20, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Qualitative or quantitative defects of delta-sarcoglycan Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Limb-girdle muscular dystrophy, recessive Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1
May 17, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
Nov 09, 2016
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L Benign:1
Feb 07, 2022
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dilated cardiomyopathy 1L Benign:1
Feb 08, 2023
Genome-Nilou Lab
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
5.8
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs10071079; hg19: chr5-156074478; COSMIC: COSV100548508; API