NM_032160.3:c.2189A>G

Variant summary

Our verdict is Benign. The variant received -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 (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0040 ( 13 hom. )

Consequence

DSEL
NM_032160.3 missense

Scores

1
8
6

Clinical Significance

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

Conservation

PhyloP100: 5.95

Publications

11 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
DSELNM_032160.3 linkc.2189A>G p.Tyr730Cys 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
DSELENST00000310045.9 linkc.2189A>G p.Tyr730Cys missense_variant Exon 2 of 2 2 NM_032160.3 ENSP00000310565.8 Q8IZU8
ENSG00000263424ENST00000583493.1 linkn.1679T>C non_coding_transcript_exon_variant Exon 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.00291
AC:
443
AN:
152218
Hom.:
1
Cov.:
33
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
GnomAD2 exomes
AF:
0.00344
AC:
863
AN:
250930
AF XY:
0.00375
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 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.:
13
Cov.:
34
AF XY:
0.00392
AC XY:
2853
AN XY:
727208
show subpopulations
African (AFR)
AF:
0.000657
AC:
22
AN:
33480
American (AMR)
AF:
0.00275
AC:
123
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00138
AC:
36
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00135
AC:
116
AN:
86238
European-Finnish (FIN)
AF:
0.00640
AC:
342
AN:
53416
Middle Eastern (MID)
AF:
0.00208
AC:
12
AN:
5768
European-Non Finnish (NFE)
AF:
0.00446
AC:
4954
AN:
1111996
Other (OTH)
AF:
0.00361
AC:
218
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
341
682
1022
1363
1704
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
170
340
510
680
850
<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:
0.00291
AC:
443
AN:
152336
Hom.:
1
Cov.:
33
AF XY:
0.00275
AC XY:
205
AN XY:
74498
show subpopulations
African (AFR)
AF:
0.000553
AC:
23
AN:
41584
American (AMR)
AF:
0.00209
AC:
32
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00144
AC:
5
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.000621
AC:
3
AN:
4832
European-Finnish (FIN)
AF:
0.00480
AC:
51
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00457
AC:
311
AN:
68026
Other (OTH)
AF:
0.00378
AC:
8
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
28
56
83
111
139
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00384
Hom.:
5
Bravo
AF:
0.00276
TwinsUK
AF:
0.00485
AC:
18
ALSPAC
AF:
0.00623
AC:
24
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00349
AC:
30
ExAC
AF:
0.00359
AC:
436
Asia WGS
AF:
0.000577
AC:
2
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
Dec 19, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
26
DANN
Uncertain
1.0
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.93
T
PhyloP100
5.9
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.33
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Vest4
0.88
MVP
0.44
MPC
0.64
ClinPred
0.036
T
GERP RS
5.1
gMVP
0.92
Mutation Taster
=67/33
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

Publications

Other links and lift over

dbSNP: rs12953840; hg19: chr18-65179657; API