18-67512115-T-C

Variant names:

• chr18-67512115-T-C
• rs35479856
• NM_032160.3:c.2494A>G

Variant summary

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

The NM_032160.3(DSEL):​c.2494A>G​(p.Thr832Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 33)
• Consequence: DSEL NM_032160.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

Genes affected

DSEL (HGNC:18144): (dermatan sulfate epimerase like) Predicted to enable chondroitin-glucuronate 5-epimerase activity. Predicted to be involved in chondroitin sulfate metabolic process and dermatan sulfate metabolic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263424 (HGNC:):

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 (MetaRNN=0.039249897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032160.3. 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
	DSEL	NM_032160.3	MANE Select	c.2494A>G	p.Thr832Ala	missense	Exon 2 of 2	NP_115536.2	Q8IZU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSEL	ENST00000310045.9	TSL:2 MANE Select	c.2494A>G	p.Thr832Ala	missense	Exon 2 of 2	ENSP00000310565.8	Q8IZU8
	DSEL	ENST00000933112.1		c.2494A>G	p.Thr832Ala	missense	Exon 2 of 2	ENSP00000603171.1
	DSEL	ENST00000933113.1		c.2494A>G	p.Thr832Ala	missense	Exon 3 of 3	ENSP00000603172.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.6
DANN	Benign	0.85
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.0090
Sift	Benign	0.74	T
Sift4G	Benign	0.35	T
Vest4		0.016
MVP		0.048
MPC		0.12
ClinPred		0.037	T
GERP RS		2.8
gMVP		0.46
Mutation Taster		=88/12	polymorphism

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: rs35479856; hg19: chr18-65179352;