dbSNP rs1801193: SGCD:p.Tyr28Tyr (chr5-156344569-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000337.6(SGCD):c.84T>C(p.Tyr28Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,610,812 control chromosomes in the GnomAD database, including 164,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13481 hom., cov: 31)

Exomes 𝑓: 0.45 ( 150965 hom. )

Consequence

SGCD
NM_000337.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.334

Publications

22 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 Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2F
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 5-156344569-T-C is Benign according to our data. Variant chr5-156344569-T-C is described in ClinVar as Benign. ClinVar VariationId is 48125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.334 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

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
SGCD	NM_000337.6	MANE Select	c.84T>C	p.Tyr28Tyr	synonymous	Exon 3 of 9	NP_000328.2
SGCD	NM_001128209.2		c.81T>C	p.Tyr27Tyr	synonymous	Exon 2 of 8	NP_001121681.1
SGCD	NM_172244.3		c.84T>C	p.Tyr28Tyr	synonymous	Exon 3 of 8	NP_758447.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGCD	ENST00000337851.9	TSL:1 MANE Select	c.84T>C	p.Tyr28Tyr	synonymous	Exon 3 of 9	ENSP00000338343.4
SGCD	ENST00000435422.7	TSL:1	c.81T>C	p.Tyr27Tyr	synonymous	Exon 2 of 8	ENSP00000403003.2
SGCD	ENST00000959784.1		c.84T>C	p.Tyr28Tyr	synonymous	Exon 3 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61982

AN:

151814

Hom.:

13485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.480

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.429

GnomAD2 exomes

AF:

0.469

AC:

115786

AN:

247132

AF XY:

0.475

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.444

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.448

AC:

654227

AN:

1458880

Hom.:

150965

Cov.:

AF XY:

0.452

AC XY:

328256

AN XY:

725632

show subpopulations

African (AFR)

AF:

0.258

AC:

8596

AN:

33376

American (AMR)

AF:

0.446

AC:

19865

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

12539

AN:

26080

East Asian (EAS)

AF:

0.795

AC:

31429

AN:

39550

South Asian (SAS)

AF:

0.557

AC:

47761

AN:

85730

European-Finnish (FIN)

AF:

0.456

AC:

24341

AN:

53394

Middle Eastern (MID)

AF:

0.497

AC:

2865

AN:

5764

European-Non Finnish (NFE)

AF:

0.432

AC:

479263

AN:

1110212

Other (OTH)

AF:

0.457

AC:

27568

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16996

33991

50987

67982

84978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14802

29604

44406

59208

74010

<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:

0.408

AC:

62003

AN:

151932

Hom.:

13481

Cov.:

AF XY:

0.417

AC XY:

30989

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.269

AC:

11125

AN:

41412

American (AMR)

AF:

0.446

AC:

6802

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

1665

AN:

3472

East Asian (EAS)

AF:

0.793

AC:

4095

AN:

5164

South Asian (SAS)

AF:

0.548

AC:

2636

AN:

4810

European-Finnish (FIN)

AF:

0.462

AC:

4880

AN:

10554

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29336

AN:

67956

Other (OTH)

AF:

0.434

AC:

909

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1804

3608

5411

7215

9019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.419

Hom.:

8929

Bravo

AF:

0.401

Asia WGS

AF:

0.625

AC:

2174

AN:

3478

EpiCase

AF:

0.442

EpiControl

AF:

0.442

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

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

Inborn genetic diseases (1)

Limb-girdle muscular dystrophy, recessive (1)

Qualitative or quantitative defects of delta-sarcoglycan (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.1

(source)

DANN

Benign

0.48

PhyloP100

-0.33

Mutation Taster

=93/7

polymorphism (auto)

(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