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GeneBe

X-153504722-G-T

Variant summary

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

The NM_001711.6(BGN):c.91G>T(p.Asp31Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,887 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D31N) has been classified 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

11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
BGNNM_001711.6 linkuse as main transcriptc.91G>T p.Asp31Tyr missense_variant 2/8 ENST00000331595.9
BGNXM_017029724.3 linkuse as main transcriptc.91G>T p.Asp31Tyr missense_variant 1/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BGNENST00000331595.9 linkuse as main transcriptc.91G>T p.Asp31Tyr missense_variant 2/81 NM_001711.6 P1
BGNENST00000431891.1 linkuse as main transcriptc.91G>T p.Asp31Tyr missense_variant 2/55
BGNENST00000472615.5 linkuse as main transcriptn.235G>T non_coding_transcript_exon_variant 2/85
BGNENST00000480756.1 linkuse as main transcriptn.233G>T non_coding_transcript_exon_variant 2/85

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097887
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
363333
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
Bravo
AF:
0.00000378

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 testingInvitaeJan 23, 2024This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 31 of the BGN protein (p.Asp31Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BGN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Benign
-0.13
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.85
T;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.52
D;D
MetaSVM
Benign
-0.39
T
MutationAssessor
Uncertain
2.5
M;.
MutationTaster
Benign
1.0
D;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.98
D;.
Vest4
0.62
MutPred
0.52
Loss of disorder (P = 0.0393);Loss of disorder (P = 0.0393);
MVP
0.80
MPC
0.88
ClinPred
0.96
D
GERP RS
4.7
Varity_R
0.38
gMVP
0.75

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.

Other links and lift over

dbSNP: rs1011782727; hg19: chrX-152770180; API