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GeneBe

X-153504699-G-C

Variant summary

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

The NM_001711.6(BGN):c.68G>C(p.Gly23Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

BGN
NM_001711.6 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847
Variant links:
Genes affected
BGN (HGNC:1044): (biglycan) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues. This protein may also regulate inflammation and innate immunity. Additionally, the encoded protein may contribute to atherosclerosis and aortic valve stenosis in human patients. This gene and the related gene decorin are thought to be the result of a gene duplication. [provided by RefSeq, Nov 2015]

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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=0.18943512).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BGNNM_001711.6 linkuse as main transcriptc.68G>C p.Gly23Ala missense_variant 2/8 ENST00000331595.9
BGNXM_017029724.3 linkuse as main transcriptc.68G>C p.Gly23Ala missense_variant 1/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BGNENST00000331595.9 linkuse as main transcriptc.68G>C p.Gly23Ala missense_variant 2/81 NM_001711.6 P1
BGNENST00000431891.1 linkuse as main transcriptc.68G>C p.Gly23Ala missense_variant 2/55
BGNENST00000472615.5 linkuse as main transcriptn.212G>C non_coding_transcript_exon_variant 2/85
BGNENST00000480756.1 linkuse as main transcriptn.210G>C non_coding_transcript_exon_variant 2/85

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD3 exomes
AF:
0.00000546
AC:
1
AN:
183243
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67747
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097929
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
363369
show subpopulations
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:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeAug 08, 2020In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BGN-related conditions. This variant is present in population databases (rs782728797, ExAC 0.02%). This sequence change replaces glycine with alanine at codon 23 of the BGN protein (p.Gly23Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.41
Cadd
Benign
17
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D;T
FATHMM_MKL
Benign
0.55
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.10
Sift
Benign
0.085
T;D
Sift4G
Benign
0.19
T;T
Polyphen
0.18
B;.
Vest4
0.12
MutPred
0.51
Gain of catalytic residue at G23 (P = 0.0556);Gain of catalytic residue at G23 (P = 0.0556);
MVP
0.78
MPC
0.37
ClinPred
0.25
T
GERP RS
3.9
Varity_R
0.34
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs782728797; hg19: chrX-152770157; API