Variant 1-155040507-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152494.4(DCST1):c.414C>G(p.His138Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DCST1
NM_152494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36426628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4 linkuse as main transcript	c.414C>G	p.His138Gln	missense_variant	6/17	ENST00000295542.6	NP_689707.2	Q5T197-1B4DXB8B4DXE3
DCST1	NM_001143687.2 linkuse as main transcript	c.339C>G	p.His113Gln	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.414C>G	p.His138Gln	missense_variant	6/17	2	NM_152494.4	ENSP00000295542.2	Q5T197-1
DCST1	ENST00000368419.2 linkuse as main transcript	c.414C>G	p.His138Gln	missense_variant	5/16	1		ENSP00000357404.2	Q5T197-2
DCST1	ENST00000525273.5 linkuse as main transcript	n.489C>G		non_coding_transcript_exon_variant	6/15	2		ENSP00000433667.1	E9PJX3
DCST1	ENST00000423025.6 linkuse as main transcript	c.339C>G	p.His113Gln	missense_variant	5/16	2		ENSP00000387369.2	Q5T197-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000442

AC:

AN:

226020

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121796

show subpopulations

Gnomad AFR exome

AF:

0.0000718

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000825

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

Oct 03, 2024

The c.414C>G (p.H138Q) alteration is located in exon 6 (coding exon 5) of the DCST1 gene. This alteration results from a C to G substitution at nucleotide position 414, causing the histidine (H) at amino acid position 138 to be replaced by a glutamine (Q). 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

-0.35

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.051

T;.;.

Eigen

Benign

-0.071

Eigen_PC

Benign

0.062

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.;M

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.12

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.070

B;.;.

Vest4

0.45

MutPred

0.33

Loss of catalytic residue at L140 (P = 0.0651);.;Loss of catalytic residue at L140 (P = 0.0651);

MVP

0.73

MPC

0.14

ClinPred

0.16

GERP RS

4.2

Varity_R

0.17

gMVP

0.29

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

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