X-153504683-C-G

Variant names:

• chrX-153504683-C-G
• NM_001711.6:c.52C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001711.6(BGN):​c.52C>G​(p.Pro18Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,698 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: BGN NM_001711.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.52C>G	p.Pro18Ala	missense_variant	Exon 2 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.52C>G	p.Pro18Ala	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.52C>G	p.Pro18Ala	missense_variant	Exon 2 of 8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000431891.1	c.52C>G	p.Pro18Ala	missense_variant	Exon 2 of 5	5		ENSP00000402525.1
BGN	ENST00000472615.5	n.196C>G		non_coding_transcript_exon_variant	Exon 2 of 8	5
BGN	ENST00000480756.1	n.194C>G		non_coding_transcript_exon_variant	Exon 2 of 8	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097698 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363150

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: 0.00000119

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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.55
MutPred		0.63		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.85
MPC		1.0
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.80
gMVP		0.71

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-152770141;