dbSNP rs2279269: DSEL:p.Pro673Ser (chr18-67512592-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/19 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: 𝑓 0.46 ( 17084 hom., cov: 33)

Exomes 𝑓: 0.50 ( 187183 hom. )

Consequence

DSEL
NM_032160.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Publications

29 publications found

Variant links:

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]

DSEL links:

ENSG00000263424 (HGNC:):

ENSG00000263424 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DSEL	NM_032160.3 link	c.2017C>T	p.Pro673Ser	missense_variant	Exon 2 of 2	ENST00000310045.9	NP_115536.2	Q8IZU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSEL	ENST00000310045.9 link	c.2017C>T	p.Pro673Ser	missense_variant	Exon 2 of 2	2	NM_032160.3	ENSP00000310565.8		Q8IZU8
ENSG00000263424	ENST00000583493.1 link	n.1851G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70462

AN:

151832

Hom.:

17069

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.497

AC:

124365

AN:

250402

AF XY:

0.498

show subpopulations

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 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.:

AF XY:

0.502

AC XY:

364686

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.315

AC:

10531

AN:

33470

American (AMR)

AF:

0.464

AC:

20735

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

13869

AN:

26128

East Asian (EAS)

AF:

0.534

AC:

21193

AN:

39690

South Asian (SAS)

AF:

0.404

AC:

34834

AN:

86228

European-Finnish (FIN)

AF:

0.601

AC:

32060

AN:

53386

Middle Eastern (MID)

AF:

0.537

AC:

3100

AN:

5768

European-Non Finnish (NFE)

AF:

0.511

AC:

568492

AN:

1111554

Other (OTH)

AF:

0.505

AC:

30508

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

21089

42179

63268

84358

105447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16250

32500

48750

65000

81250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.464

AC:

70493

AN:

151950

Hom.:

17084

Cov.:

AF XY:

0.467

AC XY:

34647

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.325

AC:

13456

AN:

41438

American (AMR)

AF:

0.456

AC:

6961

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1804

AN:

3472

East Asian (EAS)

AF:

0.512

AC:

2640

AN:

5152

South Asian (SAS)

AF:

0.397

AC:

1914

AN:

4816

European-Finnish (FIN)

AF:

0.604

AC:

6369

AN:

10538

Middle Eastern (MID)

AF:

0.565

AC:

165

AN:

292

European-Non Finnish (NFE)

AF:

0.525

AC:

35695

AN:

67952

Other (OTH)

AF:

0.522

AC:

1104

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1889

3777

5666

7554

9443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.504

Hom.:

71872

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

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.75

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.23

MetaRNN

Benign

0.000081

MetaSVM

Benign

-0.93

PhyloP100

1.6

PrimateAI

Benign

0.39

PROVEAN

Benign

0.70

REVEL

Benign

0.079

Sift

Benign

1.0

Sift4G

Benign

0.81

Vest4

0.0060

MPC

0.13

ClinPred

0.0038

GERP RS

2.9

gMVP

0.23

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over