rs483981

Variant names:

• chr6-116441914-T-C
• rs483981
• NM_013352.4:c.*4569T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013352.4(DSE):​c.*4569T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,152 control chromosomes in the GnomAD database, including 51,849 homozygotes. 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: 𝑓 0.82 (51840 hom., cov: 31)
  • Exomes 𝑓: 0.82 (9 hom.)
• Consequence: DSE NM_013352.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 8 publications found

Genes affected

DSE (HGNC:21144): (dermatan sulfate epimerase) The protein encoded by this gene is a tumor-rejection antigen. It is localized to the endoplasmic reticulum and functions to convert D-glucuronic acid to L-iduronic acid during the biosynthesis of dermatan sulfate. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. Mutations in this gene cause inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 9, and a paralogous gene exists on chromosome 18. [provided by RefSeq, Apr 2016]

DSE Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: G2P, ClinGen, PanelApp Australia, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285446 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013352.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	NM_013352.4	MANE Select	c.*4569T>C		3_prime_UTR	Exon 6 of 6	NP_037484.1	Q9UL01
	DSE	NM_001322939.2		c.*4569T>C		3_prime_UTR	Exon 6 of 6	NP_001309868.1	B7Z765
	DSE	NM_001080976.3		c.*4569T>C		3_prime_UTR	Exon 6 of 6	NP_001074445.1	Q9UL01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	ENST00000644252.3	MANE Select	c.*4569T>C		3_prime_UTR	Exon 6 of 6	ENSP00000494147.2	Q9UL01
	DSE	ENST00000452085.7	TSL:1	c.*4569T>C		3_prime_UTR	Exon 6 of 6	ENSP00000404049.2	Q9UL01
	ENSG00000285446	ENST00000644499.1		c.766+10721T>C		intron	N/A	ENSP00000495266.1	A0A2R8Y6J1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124411 AN: 152006 Hom.: 51786 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.821 AC: 23 AN: 28 Hom.: 9 Cov.: 0 AF XY: 0.714 AC XY: 10 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.846 AC: 22 AN: 26

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.819 AC: 124524 AN: 152124 Hom.: 51840 Cov.: 31 AF XY: 0.816 AC XY: 60646 AN XY: 74350

African (AFR) AF: 0.950 AC: 39448 AN: 41532

American (AMR) AF: 0.836 AC: 12764 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2861 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2374 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3248 AN: 4810

European-Finnish (FIN) AF: 0.789 AC: 8353 AN: 10582

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53029 AN: 67970

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.796 Hom.: 94372

Bravo AF: 0.827

Asia WGS AF: 0.623 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.53
PhyloP100		-1.2

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: rs483981; hg19: chr6-116763077;