rs9959648

Positions:

• chr18-67513469-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032160.3(DSEL):​c.1140A>G​(p.Gln380Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,614,120 control chromosomes in the GnomAD database, including 785 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 0.039 (376 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (409 hom.)
• Consequence: DSEL NM_032160.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.539 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSEL	NM_032160.3	c.1140A>G	p.Gln380Gln	synonymous_variant	2/2	ENST00000310045.9	NP_115536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSEL	ENST00000310045.9	c.1140A>G	p.Gln380Gln	synonymous_variant	2/2	2	NM_032160.3	ENSP00000310565.8
ENSG00000263424	ENST00000583493.1	n.2728T>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5850 AN: 152114 Hom.: 375 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.00985 AC: 2476 AN: 251478 Hom.: 169 AF XY: 0.00709 AC XY: 963 AN XY: 135908

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.00575

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00422 AC: 6173 AN: 1461888 Hom.: 409 Cov.: 34 AF XY: 0.00362 AC XY: 2630 AN XY: 727248

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.00682

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000233

Gnomad4 OTH exome AF: 0.00904

GnomAD4 genome AF: 0.0386 AC: 5870 AN: 152232 Hom.: 376 Cov.: 33 AF XY: 0.0359 AC XY: 2676 AN XY: 74442

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0221 Hom.: 130

Bravo AF: 0.0451

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	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: rs9959648; hg19: chr18-65180706;