5-156326872-G-A

Position:

chr5-156326872-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The ENST00000435422(SGCD):c.-361G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 152,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 0 hom. )

Consequence

SGCD
ENST00000435422 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.56

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 links:

LOC124901120 (HGNC:):

LOC124901120 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-156326872-G-A is Benign according to our data. Variant chr5-156326872-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00021 (32/152356) while in subpopulation EAS AF= 0.00598 (31/5186). AF 95% confidence interval is 0.00433. There are 1 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
SGCD	XM_017009724.2 linkuse as main transcript	c.-43-2662G>A	intron_variant	XP_016865213.1	Q92629-2
SGCD	XM_047417518.1 linkuse as main transcript	c.-43-2662G>A	intron_variant	XP_047273474.1
SGCD	XM_047417519.1 linkuse as main transcript	c.-43-2662G>A	intron_variant	XP_047273475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000435422 linkuse as main transcript	c.-361G>A		5_prime_UTR_variant	1/8	1		ENSP00000403003.2		Q92629-1
SGCD	ENST00000517913.5 linkuse as main transcript	c.-43-2662G>A		intron_variant		5		ENSP00000429378.1		Q92629-3

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00596

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00500

AC:

AN:

200

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

AN XY:

152

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00633

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000210

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00598

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000317

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2F

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Qualitative or quantitative defects of delta-sarcoglycan

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 03, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Dilated cardiomyopathy 1L

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

not specified

Other:1

not provided, no classification provided

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Dec 05, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over