rs3138167

Variant names:

• chr12-91178638-C-A
• rs3138167
• NM_001920.5:c.-33-53G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-91178638-C-A
• chr12-91178638-C-G
• chr12-91178638-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133504.3(DCN):​c.-86G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000106 in 942,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: DCN NM_133504.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 7 publications found

Genes affected

DCN (HGNC:2705): (decorin) This gene encodes a member of the small leucine-rich proteoglycan family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. This protein plays a role in collagen fibril assembly. Binding of this protein to multiple cell surface receptors mediates its role in tumor suppression, including a stimulatory effect on autophagy and inflammation and an inhibitory effect on angiogenesis and tumorigenesis. This gene and the related gene biglycan are thought to be the result of a gene duplication. Mutations in this gene are associated with congenital stromal corneal dystrophy in human patients. [provided by RefSeq, Nov 2015]

DCN Gene-Disease associations (from GenCC):

• congenital stromal corneal dystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133504.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	NM_001920.5	MANE Select	c.-33-53G>T		intron	N/A	NP_001911.1
	DCN	NM_133504.3		c.-86G>T		5_prime_UTR	Exon 1 of 5	NP_598011.1
	DCN	NM_133505.3		c.-86G>T		5_prime_UTR	Exon 1 of 4	NP_598012.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	ENST00000052754.10	TSL:1 MANE Select	c.-33-53G>T		intron	N/A	ENSP00000052754.5
	DCN	ENST00000393155.6	TSL:1	n.-33-53G>T		intron	N/A	ENSP00000376862.2
	DCN	ENST00000880707.1		c.-86G>T		5_prime_UTR	Exon 1 of 7	ENSP00000550766.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000106 AC: 1 AN: 942330 Hom.: 0 AF XY: 0.00000204 AC XY: 1 AN XY: 489594

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23132

American (AMR) AF: 0.00 AC: 0 AN: 41194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22592

East Asian (EAS) AF: 0.00 AC: 0 AN: 36764

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 644328

Other (OTH) AF: 0.00 AC: 0 AN: 43294

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.094
DANN	Benign	0.36
PhyloP100		-0.75
PromoterAI		-0.030	Neutral

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

Other links and lift over

dbSNP: rs3138167; hg19: chr12-91572415;