Variant rs12953840 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032160.3(DSEL):c.2189A>G(p.Tyr730Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00388 in 1,614,182 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 13 hom. )

Consequence

DSEL
NM_032160.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.95

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017606676).

BP6

Variant 18-67512420-T-C is Benign according to our data. Variant chr18-67512420-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 719335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSEL	NM_032160.3 linkuse as main transcript	c.2189A>G	p.Tyr730Cys	missense_variant	2/2	ENST00000310045.9	NP_115536.2	Q8IZU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSEL	ENST00000310045.9 linkuse as main transcript	c.2189A>G	p.Tyr730Cys	missense_variant	2/2	2	NM_032160.3	ENSP00000310565.8		Q8IZU8
ENSG00000263424	ENST00000583493.1 linkuse as main transcript	n.1679T>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00344

AC:

863

AN:

250930

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000808

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00527

Gnomad NFE exome

AF:

0.00503

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00398

AC:

5823

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2853

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.00640

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00291

AC:

443

AN:

152336

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.00276

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00359

AC:

436

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.030

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.93

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Vest4

0.88

MVP

0.44

MPC

0.64

ClinPred

0.036

GERP RS

5.1

gMVP

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over