5-156508589-G-T

Position:

chr5-156508589-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The ENST00000337851.9(SGCD):c.193-12G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,548,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SGCD
ENST00000337851.9 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001219

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: -0.160

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-156508589-G-T is Benign according to our data. Variant chr5-156508589-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 165231.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3}.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000229 (32/1396712) while in subpopulation EAS AF= 0.000127 (5/39290). AF 95% confidence interval is 0.0000495. There are 0 homozygotes in gnomad4_exome. There are 13 alleles in male gnomad4_exome subpopulation. Median coverage is 23. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCD	NM_000337.6 linkuse as main transcript	c.193-12G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9 linkuse as main transcript	c.193-12G>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_000337.6	ENSP00000338343	P4	Q92629-2
SGCD	ENST00000435422.7 linkuse as main transcript	c.190-12G>T	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000403003	A1	Q92629-1
SGCD	ENST00000517913.5 linkuse as main transcript	c.193-12G>T	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000429378		Q92629-3
SGCD	ENST00000524347.2 linkuse as main transcript	c.*57-12G>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	5		ENSP00000430794

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151836

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246406

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

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:

0.0000229

AC:

AN:

1396712

Hom.:

Cov.:

AF XY:

0.0000186

AC XY:

AN XY:

698936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000190

Gnomad4 OTH exome

AF:

0.000429

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00238

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000227

Asia WGS

AF:

0.00520

AC:

AN:

3474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:2Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 05, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Uncertain significance, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 05, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 03, 2014	The 193-12G>T variant in SGCD has not been previously reported in individuals wi th cardiomyopathy or in large population studies. This variant is located in the 3' splice region. Computational tools do not suggest an impact to splicing, tho ugh this information is not predictive enough to rule out pathogenicity. In summ ary, the clinical significance of the 193-12G>T variant is uncertain. -

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

May 23, 2017

- -

Autosomal recessive limb-girdle muscular dystrophy type 2F

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

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

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