Variant 1-155039510-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152494.4(DCST1):c.370G>A(p.Ala124Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,599,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

DCST1
NM_152494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19768858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4 linkuse as main transcript	c.370G>A	p.Ala124Thr	missense_variant	5/17	ENST00000295542.6	NP_689707.2	Q5T197-1B4DXB8B4DXE3
DCST1	NM_001143687.2 linkuse as main transcript	c.295G>A	p.Ala99Thr	missense_variant	4/16		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.370G>A	p.Ala124Thr	missense_variant	5/17	2	NM_152494.4	ENSP00000295542.2	Q5T197-1
DCST1	ENST00000368419.2 linkuse as main transcript	c.370G>A	p.Ala124Thr	missense_variant	4/16	1		ENSP00000357404.2	Q5T197-2
DCST1	ENST00000525273.5 linkuse as main transcript	n.445G>A		non_coding_transcript_exon_variant	5/15	2		ENSP00000433667.1	E9PJX3
DCST1	ENST00000423025.6 linkuse as main transcript	c.295G>A	p.Ala99Thr	missense_variant	4/16	2		ENSP00000387369.2	Q5T197-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000249

AC:

AN:

241394

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130518

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000625

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.0000350

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000829

AC:

AN:

1447238

Hom.:

Cov.:

AF XY:

0.00000973

AC XY:

AN XY:

719324

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000462

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000515

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000634

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

ExAC

AF:

0.0000165

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

Jun 07, 2023

The c.370G>A (p.A124T) alteration is located in exon 5 (coding exon 4) of the DCST1 gene. This alteration results from a G to A substitution at nucleotide position 370, causing the alanine (A) at amino acid position 124 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.97

D;.;.

Vest4

0.43

MutPred

0.48

Loss of catalytic residue at A124 (P = 0.4393);.;Loss of catalytic residue at A124 (P = 0.4393);

MVP

0.61

MPC

0.26

ClinPred

0.45

GERP RS

3.2

Varity_R

0.086

gMVP

0.28

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