rs768838951

Variant names:

• chr4-52038236-AGCCGCCGCC-A
• rs768838951
• NM_000232.5:c.15_23delGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr4-52038236-AGCCGCCGCC-A
• chr4-52038236-AGCCGCCGCC-AGCCGCC
• chr4-52038236-AGCCGCCGCC-AGCCGCCGCCGCC
• chr4-52038236-AGCCGCCGCC-AGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP3

The NM_000232.5(SGCB):​c.15_23delGGCGGCGGC​(p.Ala6_Ala8del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,135,466 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign. The gene SGCB is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: SGCB NM_000232.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

SGCB (HGNC:10806): (sarcoglycan beta) This gene encodes a member of the sarcoglycan family. Sarcoglycans are transmembrane components in the dystrophin-glycoprotein complex which help stabilize the muscle fiber membranes and link the muscle cytoskeleton to the extracellular matrix. Mutations in this gene have been associated with limb-girdle muscular dystrophy.[provided by RefSeq, Oct 2008]

SGCB 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 2E

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Specifications for SGCB are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 12 uncertain in NM_000232.5
• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_000232.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	NM_000232.5	MANE Select	c.15_23delGGCGGCGGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 6	NP_000223.1	Q5U0N0
	SGCB	NM_001440519.1		c.15_23delGGCGGCGGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 5	NP_001427448.1
	SGCB	NM_001440520.1		c.-393_-385delGGCGGCGGC		5_prime_UTR	Exon 1 of 7	NP_001427449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	ENST00000381431.10	TSL:1 MANE Select	c.15_23delGGCGGCGGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000370839.6	Q16585-1
	SGCB	ENST00000899666.1		c.15_23delGGCGGCGGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000569725.1
	SGCB	ENST00000912466.1		c.15_23delGGCGGCGGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 5	ENSP00000582525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000440 AC: 5 AN: 1135466 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 548178

African (AFR) AF: 0.00 AC: 0 AN: 23738

American (AMR) AF: 0.00 AC: 0 AN: 17650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16976

East Asian (EAS) AF: 0.0000806 AC: 2 AN: 24822

South Asian (SAS) AF: 0.00 AC: 0 AN: 34980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3090

European-Non Finnish (NFE) AF: 0.00000212 AC: 2 AN: 945434

Other (OTH) AF: 0.0000221 AC: 1 AN: 45152

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768838951; hg19: chr4-52904402;