rs560644

Positions:

• chr6-116436394-T-A
• chr6-116436394-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP2

The NM_013352.4(DSE):​c.1926T>A​(p.Asn642Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N642N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: DSE NM_013352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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 Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) (complex) asparagine (size 0) in uniprot entity DSE_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DSE. . Gene score misZ 2.0252 (greater than the threshold 3.09). Trascript score misZ 3.6915 (greater than threshold 3.09). GenCC has associacion of gene with Ehlers-Danlos syndrome, musculocontractural type, Ehlers-Danlos syndrome, musculocontractural type 2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSE	NM_013352.4	c.1926T>A	p.Asn642Lys	missense_variant	6/6	ENST00000644252.3	NP_037484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSE	ENST00000644252.3	c.1926T>A	p.Asn642Lys	missense_variant	6/6		NM_013352.4	ENSP00000494147	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 94

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	0.0000047	P;P;P;P
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.49	N;N;.
REVEL	Benign	0.27
Sift	Benign	0.27	T;T;.
Sift4G	Benign	0.42	T;T;.
Polyphen		1.0	D;D;D
Vest4		0.54
MVP		0.53
MPC		0.89
ClinPred		0.45	T
GERP RS		-5.2
Varity_R		0.47
gMVP		0.73

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: rs560644; hg19: chr6-116757557;