Variant 1-155041461-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152494.4(DCST1):c.596C>T(p.Ala199Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,614,076 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 26 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 14 hom. )

Consequence

DCST1
NM_152494.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.298

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003309667).

BP6

Variant 1-155041461-C-T is Benign according to our data. Variant chr1-155041461-C-T is described in ClinVar as [Benign]. Clinvar id is 789942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00875 (1333/152326) while in subpopulation AFR AF= 0.0307 (1276/41566). AF 95% confidence interval is 0.0293. There are 26 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	7/17	ENST00000295542.6	NP_689707.2	Q5T197-1B4DXB8B4DXE3
DCST1	NM_001143687.2 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	6/16		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.596C>T	p.Ala199Val	missense_variant	7/17	2	NM_152494.4	ENSP00000295542.2	Q5T197-1
DCST1	ENST00000368419.2 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	6/16	1		ENSP00000357404.2	Q5T197-2
DCST1	ENST00000525273.5 linkuse as main transcript	n.671C>T		non_coding_transcript_exon_variant	7/15	2		ENSP00000433667.1	E9PJX3
DCST1	ENST00000423025.6 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	6/16	2		ENSP00000387369.2	Q5T197-3

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1334

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.000220

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00211

AC:

531

AN:

251172

Hom.:

AF XY:

0.00151

AC XY:

205

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0293

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000883

AC:

1291

AN:

1461750

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

553

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00875

AC:

1333

AN:

152326

Hom.:

Cov.:

AF XY:

0.00843

AC XY:

628

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.00909

ESP6500AA

AF:

0.0313

AC:

138

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00265

AC:

322

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.32

MVP

0.35

MPC

0.12

ClinPred

0.013

GERP RS

-1.6

Varity_R

0.039

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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