rs782728797

Variant names:

• chrX-153504699-G-A
• NM_001711.6:c.68G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153504699-G-A
• chrX-153504699-G-C

Variant summary

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

The NM_001711.6(BGN):​c.68G>A​(p.Gly23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. G23A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: BGN NM_001711.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847

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

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 rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.68G>A	p.Gly23Asp	missense_variant	Exon 2 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.68G>A	p.Gly23Asp	missense_variant	Exon 1 of 7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.68G>A	p.Gly23Asp	missense_variant	Exon 2 of 8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000431891.1	c.68G>A	p.Gly23Asp	missense_variant	Exon 2 of 5	5		ENSP00000402525.1
BGN	ENST00000472615.5	n.212G>A		non_coding_transcript_exon_variant	Exon 2 of 8	5
BGN	ENST00000480756.1	n.210G>A		non_coding_transcript_exon_variant	Exon 2 of 8	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097929 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363369

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: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;T
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.99	D;.
Vest4		0.50
MutPred		0.52		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.83
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.77
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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-152770157;