4-52038232-C-T

Variant names:

• chr4-52038232-C-T
• rs1448040082
• NM_000232.5:c.28G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000232.5(SGCB):​c.28G>A​(p.Glu10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,286,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SGCB NM_000232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28092617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCB	NM_000232.5	c.28G>A	p.Glu10Lys	missense_variant	Exon 1 of 6	ENST00000381431.10	NP_000223.1
SGCB	XM_047416074.1	c.28G>A	p.Glu10Lys	missense_variant	Exon 1 of 5		XP_047272030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCB	ENST00000381431.10	c.28G>A	p.Glu10Lys	missense_variant	Exon 1 of 6	1	NM_000232.5	ENSP00000370839.6
SGCB	ENST00000506357.5	n.13G>A		non_coding_transcript_exon_variant	Exon 1 of 5	5		ENSP00000421235.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151228 Hom.: 0 Cov.: 32

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: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1135578 Hom.: 0 Cov.: 31 AF XY: 0.00000182 AC XY: 1 AN XY: 548368

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: 0.0000285

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151228 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73828

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: 0.0000296

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000132 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.0099	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.17
Sift	Benign	0.25	T
Sift4G	Benign	0.11	T
Polyphen		0.032	B
Vest4		0.18
MutPred		0.23		Gain of MoRF binding (P = 0.0013);
MVP		0.85
MPC		0.071
ClinPred		0.32	T
GERP RS		2.9
Varity_R		0.10
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1448040082; hg19: chr4-52904398;