rs143106297

Variant names:

• chr4-52029863-T-C
• rs143106297
• NM_000232.5:c.244A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001440520.1(SGCB):​c.-54A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000959 in 1,460,394 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 Uncertain significance (★★). The gene SGCB is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SGCB NM_001440520.1 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0004836
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: 6.07
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36659256).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440520.1. 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.244A>G	p.Ile82Val	missense splice_region	Exon 3 of 6	NP_000223.1	Q5U0N0
	SGCB	NM_001440520.1		c.-54A>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 7	NP_001427449.1
	SGCB	NM_001440519.1		c.34A>G	p.Ile12Val	missense splice_region	Exon 2 of 5	NP_001427448.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	ENST00000381431.10	TSL:1 MANE Select	c.244A>G	p.Ile82Val	missense splice_region	Exon 3 of 6	ENSP00000370839.6	Q16585-1
	SGCB	ENST00000899666.1		c.244A>G	p.Ile82Val	missense splice_region	Exon 3 of 6	ENSP00000569725.1
	SGCB	ENST00000912466.1		c.244A>G	p.Ile82Val	missense splice_region	Exon 3 of 5	ENSP00000582525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251418 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460394 Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9 AN XY: 726620

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110690

Other (OTH) AF: 0.0000332 AC: 2 AN: 60330

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Autosomal recessive limb-girdle muscular dystrophy type 2E (2)
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	0.0048	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Benign	1.7	L
PhyloP100		6.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.49
Sift	Benign	0.19	T
Sift4G	Benign	0.36	T
Polyphen		0.78	P
Vest4		0.31
MVP		0.64
MPC		0.11
ClinPred		0.50	D
GERP RS		4.0
Varity_R		0.11
gMVP		0.53
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00048
dbscSNV1_RF	Benign	0.090
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

Other links and lift over

dbSNP: rs143106297; hg19: chr4-52896029;