5-156508698-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000337.6(SGCD):​c.290G>T​(p.Arg97Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000705 in 1,417,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R97Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SGCD
NM_000337.6 missense

Scores

4
10
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.20
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SGCDNM_000337.6 linkc.290G>T p.Arg97Leu missense_variant Exon 4 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.290G>T p.Arg97Leu missense_variant Exon 4 of 9 1 NM_000337.6 ENSP00000338343.4 Q92629-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.05e-7
AC:
1
AN:
1417682
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
706330
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.93
.;D;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.78
D;D;D
MetaSVM
Uncertain
0.41
D
MutationAssessor
Benign
1.8
.;L;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.4
D;D;D
REVEL
Uncertain
0.58
Sift
Benign
0.081
T;D;D
Sift4G
Benign
0.074
T;T;T
Polyphen
0.95
P;P;P
Vest4
0.70
MutPred
0.58
.;Gain of catalytic residue at Q94 (P = 0.0483);.;
MVP
0.87
MPC
0.21
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.57
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-155935708; API