chrX-153505893-A-G

Variant names:

• chrX-153505893-A-G
• NM_001711.6:c.382A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001711.6(BGN):​c.382A>G​(p.Lys128Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K128M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: BGN NM_001711.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23748675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.382A>G	p.Lys128Glu	missense_variant	Exon 4 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.382A>G	p.Lys128Glu	missense_variant	Exon 3 of 7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.382A>G	p.Lys128Glu	missense_variant	Exon 4 of 8	1	NM_001711.6	ENSP00000327336.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.24
Sift	Benign	0.097	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.0080	B;.
Vest4		0.47
MutPred		0.44		Loss of MoRF binding (P = 0.0074);.;
MVP		0.92
MPC		0.52
ClinPred		0.38	T
GERP RS		4.7
Varity_R		0.68
gMVP		0.47
Mutation Taster		=51/49	polymorphism

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152771351;