Variant chr1-155040580-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_152494.4(DCST1):c.487C>T(p.Arg163Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,586,568 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

DCST1
NM_152494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4 linkuse as main transcript	c.487C>T	p.Arg163Cys	missense_variant	6/17	ENST00000295542.6	NP_689707.2	Q5T197-1B4DXB8B4DXE3
DCST1	NM_001143687.2 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	5/16		NP_001137159.1	Q5T197-3B4DXB8B4DXE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCST1	ENST00000295542.6 linkuse as main transcript	c.487C>T	p.Arg163Cys	missense_variant	6/17	2	NM_152494.4	ENSP00000295542.2	Q5T197-1
DCST1	ENST00000368419.2 linkuse as main transcript	c.487C>T	p.Arg163Cys	missense_variant	5/16	1		ENSP00000357404.2	Q5T197-2
DCST1	ENST00000525273.5 linkuse as main transcript	n.562C>T		non_coding_transcript_exon_variant	6/15	2		ENSP00000433667.1	E9PJX3
DCST1	ENST00000423025.6 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	5/16	2		ENSP00000387369.2	Q5T197-3

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000287

AC:

AN:

205578

Hom.:

AF XY:

0.000271

AC XY:

AN XY:

110566

show subpopulations

Gnomad AFR exome

AF:

0.0000800

Gnomad AMR exome

AF:

0.000430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000486

Gnomad OTH exome

AF:

0.000380

GnomAD4 exome

AF:

0.000446

AC:

639

AN:

1434236

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

316

AN XY:

710934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000911

Gnomad4 AMR exome

AF:

0.000435

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000527

Gnomad4 OTH exome

AF:

0.000658

GnomAD4 genome

AF:

0.000617

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000536

Hom.:

Bravo

AF:

0.000884

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000207

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.487C>T (p.R163C) alteration is located in exon 6 (coding exon 5) of the DCST1 gene. This alteration results from a C to T substitution at nucleotide position 487, causing the arginine (R) at amino acid position 163 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;.

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.61

MVP

0.77

MPC

0.59

ClinPred

0.22

GERP RS

3.6

Varity_R

0.17

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: -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