rs752548592

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_000337.6(SGCD):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,606,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SGCD
NM_000337.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:10

Conservation

PhyloP100: 9.86

Publications

6 publications found

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]

SGCD Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
autosomal recessive limb-girdle muscular dystrophy type 2F
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
dilated cardiomyopathy 1L
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

SGCD links:

LOC124901120 (HGNC:):

LOC124901120 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000199 (29/1454912) while in subpopulation MID AF = 0.000523 (3/5738). AF 95% confidence interval is 0.000142. There are 0 homozygotes in GnomAdExome4. There are 11 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000337.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCD	NM_000337.6	MANE Select	c.32G>A	p.Arg11Gln	missense	Exon 3 of 9	NP_000328.2
SGCD	NM_001128209.2		c.29G>A	p.Arg10Gln	missense	Exon 2 of 8	NP_001121681.1	Q92629-1
SGCD	NM_172244.3		c.32G>A	p.Arg11Gln	missense	Exon 3 of 8	NP_758447.1	Q92629-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCD	ENST00000337851.9	TSL:1 MANE Select	c.32G>A	p.Arg11Gln	missense	Exon 3 of 9	ENSP00000338343.4	Q92629-2
SGCD	ENST00000435422.7	TSL:1	c.29G>A	p.Arg10Gln	missense	Exon 2 of 8	ENSP00000403003.2	Q92629-1
SGCD	ENST00000959784.1		c.32G>A	p.Arg11Gln	missense	Exon 3 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

243066

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1454912

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

723484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33132

American (AMR)

AF:

0.00

AC:

AN:

43894

Ashkenazi Jewish (ASJ)

AF:

0.0000768

AC:

AN:

26026

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39138

South Asian (SAS)

AF:

0.0000709

AC:

AN:

84588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1108932

Other (OTH)

AF:

0.00

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41302

American (AMR)

AF:

0.0000656

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive limb-girdle muscular dystrophy type 2F (3)

not provided (3)

Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L (2)

Dilated cardiomyopathy 1L (1)

Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

0.0046

MutationAssessor

Benign

0.69

PhyloP100

9.9

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.17

REVEL

Benign

0.28

Sift

Benign

0.34

Sift4G

Benign

0.59

Polyphen

1.0

Vest4

0.66

MutPred

0.11

Gain of glycosylation at S11 (P = 0.0757)

MVP

0.81

MPC

0.19

ClinPred

0.51

GERP RS

5.6

Varity_R

0.15

gMVP

0.56

Mutation Taster

=41/59

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over