chr18-67512592-G-A

Position:

• chr18-67512592-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032160.3(DSEL):​c.2017C>T​(p.Pro673Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,613,254 control chromosomes in the GnomAD database, including 204,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.46 (17084 hom., cov: 33)
  • Exomes 𝑓: 0.50 (187183 hom.)
• Consequence: DSEL NM_032160.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.1463484E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSEL	NM_032160.3	c.2017C>T	p.Pro673Ser	missense_variant	2/2	ENST00000310045.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSEL	ENST00000310045.9	c.2017C>T	p.Pro673Ser	missense_variant	2/2	2	NM_032160.3	P1
	ENST00000583493.1	n.1851G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70462 AN: 151832 Hom.: 17069 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.517

GnomAD3 exomes AF: 0.497 AC: 124365 AN: 250402 Hom.: 31680 AF XY: 0.498 AC XY: 67418 AN XY: 135404

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.531

Gnomad EAS exome AF: 0.521

Gnomad SAS exome AF: 0.402

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.503 AC: 735322 AN: 1461304 Hom.: 187183 Cov.: 46 AF XY: 0.502 AC XY: 364686 AN XY: 726996

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.464 AC: 70493 AN: 151950 Hom.: 17084 Cov.: 33 AF XY: 0.467 AC XY: 34647 AN XY: 74256

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.522

Alfa AF: 0.515 Hom.: 47031

Bravo AF: 0.450

TwinsUK AF: 0.507 AC: 1881

ALSPAC AF: 0.502 AC: 1934

ESP6500AA AF: 0.324 AC: 1427

ESP6500EA AF: 0.517 AC: 4444

ExAC AF: 0.493 AC: 59888

Asia WGS AF: 0.460 AC: 1599 AN: 3478

EpiCase AF: 0.546

EpiControl AF: 0.536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.75
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.23	N
MetaRNN	Benign	0.000081	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.70	N
REVEL	Benign	0.079
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Vest4		0.0060
MPC		0.13
ClinPred		0.0038	T
GERP RS		2.9
gMVP		0.23

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: rs2279269; hg19: chr18-65179829; COSMIC: COSV59491011; COSMIC: COSV59491011;