13-23203692-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

This summary comes from the ClinGen Evidence Repository: The NM_000231.3: c.1-3C>T variant is an intronic SGCG variant that is located in a splice region. The computational splicing predictor SpliceAI gives a score of 0.02 for acceptor loss, suggesting that the variant has no impact on splicing since it does not exceed the designated LGMD VCEP threshold (≤0.05) (BP4). The highest minor allele frequency of this variant is 0.0003793 (6/15820 exome chromosomes) in the African/African American population in gnomAD v2.1.1, which is greater than the ClinGen LGMD threshold (≤0.00009) for PM2_Supporting, and therefore does not meet this criterion (PM2_Supporting, BA1, BS1 criteria not met). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Limb-Girdle Muscular Dystrophy VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA6909546/MONDO:0015152/185

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SGCG
NM_000231.3 splice_region, intron

Scores

2
Splicing: ADA: 0.04313
2

Clinical Significance

Likely benign reviewed by expert panel U:3B:1

Conservation

PhyloP100: 2.67
Variant links:
Genes affected
SGCG (HGNC:10809): (sarcoglycan gamma) This gene encodes gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C). [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SGCGNM_000231.3 linkc.1-3C>T splice_region_variant, intron_variant ENST00000218867.4 NP_000222.2 Q13326

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SGCGENST00000218867.4 linkc.1-3C>T splice_region_variant, intron_variant 1 NM_000231.3 ENSP00000218867.3 Q13326

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000244
AC:
6
AN:
245446
Hom.:
0
AF XY:
0.00000755
AC XY:
1
AN XY:
132476
show subpopulations
Gnomad AFR exome
AF:
0.000379
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1457276
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
724690
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.0000756

ClinVar

Significance: Likely benign
Submissions summary: Uncertain:3Benign:1
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2C Uncertain:2
Uncertain significance, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Uncertain significance, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsNov 10, 2021- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAthena DiagnosticsJun 18, 2019- -
Autosomal recessive limb-girdle muscular dystrophy Benign:1
Likely benign, reviewed by expert panelcurationClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGenJan 08, 2025The NM_000231.3: c.1-3C>T variant is an intronic SGCG variant that is located in a splice region. The computational splicing predictor SpliceAI gives a score of 0.02 for acceptor loss, suggesting that the variant has no impact on splicing since it does not exceed the designated LGMD VCEP threshold (≤0.05) (BP4). The highest minor allele frequency of this variant is 0.0003793 (6/15820 exome chromosomes) in the African/African American population in gnomAD v2.1.1, which is greater than the ClinGen LGMD threshold (≤0.00009) for PM2_Supporting, and therefore does not meet this criterion (PM2_Supporting, BA1, BS1 criteria not met). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Limb-Girdle Muscular Dystrophy VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): BP4. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
9.4
DANN
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.043
dbscSNV1_RF
Benign
0.34
SpliceAI score (max)
0.020
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: rs373335254; hg19: chr13-23777831; API