rs483981

Positions:

• chr6-116441914-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSE	NM_013352.4	c.*4569T>C		3_prime_UTR_variant	6/6	ENST00000644252.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSE	ENST00000644252.3	c.*4569T>C		3_prime_UTR_variant	6/6		NM_013352.4	P1
DSE	ENST00000452085.7	c.*4569T>C		3_prime_UTR_variant	6/6	1		P1

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

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.500

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

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.783

Alfa AF: 0.793 Hom.: 67360

Bravo AF: 0.827

Asia WGS AF: 0.623 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

LitVar

Other links and lift over

dbSNP: rs483981; hg19: chr6-116763077;