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.

• 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 Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2E

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

ACMG classification

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
	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
	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;