Variant 4-52038232-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000232.5(SGCB):c.28G>C(p.Glu10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SGCB
NM_000232.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.615

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24917862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCB	NM_000232.5 linkuse as main transcript	c.28G>C	p.Glu10Gln	missense_variant	1/6	ENST00000381431.10	NP_000223.1
SGCB	XM_047416074.1 linkuse as main transcript	c.28G>C	p.Glu10Gln	missense_variant	1/5		XP_047272030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCB	ENST00000381431.10 linkuse as main transcript	c.28G>C	p.Glu10Gln	missense_variant	1/6	1	NM_000232.5	ENSP00000370839	P1	Q16585-1
SGCB	ENST00000506357.5 linkuse as main transcript	c.16G>C	p.Glu6Gln	missense_variant, NMD_transcript_variant	1/5	5		ENSP00000421235

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151228

Hom.:

Cov.:

show subpopulations

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1135578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73828

show subpopulations

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.33

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.092

MutationAssessor

Benign

0.76

MutationTaster

Benign

0.95

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.61

REVEL

Benign

0.24

Sift

Benign

0.19

Sift4G

Benign

0.10

Polyphen

0.0020

Vest4

0.15

MutPred

0.057

Gain of MoRF binding (P = 0.0342);

MVP

0.87

MPC

0.063

ClinPred

0.11

GERP RS

2.9

Varity_R

0.13

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over