NM_152494.4:c.1894C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152494.4(DCST1):c.1894C>A(p.His632Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,594,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

DCST1
NM_152494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.402

Publications

1 publications found

Variant links:

Genes affected

DCST1 (HGNC:26539): (DC-STAMP domain containing 1) This gene encodes a protein with a domain similar to one found in dendritic cells (PMID:11169400) which play a key role in antigen processing and display for immune responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

DCST1 links:

DCST1-AS1 (HGNC:41147): (DCST1 antisense RNA 1)

DCST1-AS1 links:

ADAM15 (HGNC:193): (ADAM metallopeptidase domain 15) The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as a EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ADAM15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12861553).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152494.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCST1	NM_152494.4	MANE Select	c.1894C>A	p.His632Asn	missense	Exon 17 of 17	NP_689707.2	Q5T197-1
DCST1	NM_001143687.2		c.1819C>A	p.His607Asn	missense	Exon 16 of 16	NP_001137159.1	Q5T197-3
DCST1-AS1	NR_040772.1		n.525G>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCST1	ENST00000295542.6	TSL:2 MANE Select	c.1894C>A	p.His632Asn	missense	Exon 17 of 17	ENSP00000295542.2	Q5T197-1
DCST1	ENST00000423025.6	TSL:2	c.1819C>A	p.His607Asn	missense	Exon 16 of 16	ENSP00000387369.2	Q5T197-3
DCST1-AS1	ENST00000452962.2	TSL:2	n.532G>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000227

AC:

AN:

219974

AF XY:

0.0000246

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1442048

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

716688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33134

American (AMR)

AF:

0.000204

AC:

AN:

44124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39158

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5230

European-Non Finnish (NFE)

AF:

0.00000813

AC:

AN:

1106516

Other (OTH)

AF:

0.0000335

AC:

AN:

59642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000985

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41470

American (AMR)

AF:

0.000916

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.0000252

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.017

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.67

M_CAP

Benign

0.0092

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

PhyloP100

0.40

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.0

REVEL

Benign

0.047

Sift

Benign

0.17

Sift4G

Benign

0.16

Polyphen

0.045

Vest4

0.42

MutPred

0.32

Gain of helix (P = 0.0325)

MVP

0.29

MPC

0.14

ClinPred

0.12

GERP RS

1.6

Varity_R

0.10

gMVP

0.35

Mutation Taster

=86/14

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over