rs768838951

chr4-52038236-AGCCGCCGCC-Achr4-52038236-AGCCGCCGCC-AGCCGCCchr4-52038236-AGCCGCCGCC-AGCCGCCGCCGCCchr4-52038236-AGCCGCCGCC-AGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000232.5(SGCB):c.15_23del(p.Ala7_Ala9del) variant causes a 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 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCB	NM_000232.5	c.15_23del	p.Ala7_Ala9del	inframe_deletion	1/6	ENST00000381431.10
SGCB	XM_047416074.1	c.15_23del	p.Ala7_Ala9del	inframe_deletion	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCB	ENST00000381431.10	c.15_23del	p.Ala7_Ala9del	inframe_deletion	1/6	1	NM_000232.5	P1
SGCB	ENST00000506357.5	c.1_9del	p.Ala3_Ala5del	inframe_deletion, NMD_transcript_variant	1/5	5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000806

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000212

Gnomad4 OTH exome AF: 0.0000221

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs768838951; hg19: chr4-52904402;