dbSNP rs62620995: DCSTAMP:p.Leu397Phe (chr8-104355036-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_030788.4(DCSTAMP):c.1189C>T(p.Leu397Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,074 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.0091 ( 13 hom., cov: 32)

Exomes 𝑓: 0.012 ( 142 hom. )

Consequence

DCSTAMP
NM_030788.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.648

Publications

13 publications found

Variant links:

Genes affected

DCSTAMP (HGNC:18549): (dendrocyte expressed seven transmembrane protein) This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

DCSTAMP links:

DPYS (HGNC:3013): (dihydropyrimidinase) Dihydropyrimidinase catalyzes the conversion of 5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism. Dihydropyrimidinase is expressed at a high level in liver and kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript. Defects in the DPYS gene are linked to dihydropyrimidinuria. [provided by RefSeq, Jul 2008]

DPYS Gene-Disease associations (from GenCC):

dihydropyrimidinuria
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

DPYS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007275045).

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCSTAMP	NM_030788.4 link	c.1189C>T	p.Leu397Phe	missense_variant	Exon 3 of 4	ENST00000297581.2	NP_110415.1	Q9H295-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCSTAMP	ENST00000297581.2 link	c.1189C>T	p.Leu397Phe	missense_variant	Exon 3 of 4	1	NM_030788.4	ENSP00000297581.2		Q9H295-1

Frequencies

GnomAD3 genomes

AF:

0.00914

AC:

1391

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.00911

GnomAD2 exomes

AF:

0.00867

AC:

2180

AN:

251382

AF XY:

0.00875

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.0121

AC:

17704

AN:

1461840

Hom.:

142

Cov.:

AF XY:

0.0119

AC XY:

8638

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

33478

American (AMR)

AF:

0.00510

AC:

228

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000995

AC:

AN:

26136

East Asian (EAS)

AF:

0.000403

AC:

AN:

39698

South Asian (SAS)

AF:

0.00576

AC:

497

AN:

86256

European-Finnish (FIN)

AF:

0.00996

AC:

532

AN:

53418

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0142

AC:

15741

AN:

1111968

Other (OTH)

AF:

0.00969

AC:

585

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

938

1876

2814

3752

4690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.00914

AC:

1391

AN:

152234

Hom.:

Cov.:

AF XY:

0.00930

AC XY:

692

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00272

AC:

113

AN:

41532

American (AMR)

AF:

0.00837

AC:

128

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00456

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0103

AC:

109

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0145

AC:

986

AN:

68012

Other (OTH)

AF:

0.00901

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0123

Hom.:

Bravo

AF:

0.00822

TwinsUK

AF:

0.0167

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0124

AC:

107

ExAC

AF:

0.00921

AC:

1118

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

Eigen

Benign

0.10

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

0.65

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.96

REVEL

Benign

0.16

Sift

Benign

0.088

Sift4G

Pathogenic

0.0

Polyphen

0.78

Vest4

0.46

MVP

0.53

MPC

0.33

ClinPred

0.024

GERP RS

5.4

Varity_R

0.18

gMVP

0.72

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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