chr1-155034073-C-G

Position:

• chr1-155034073-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152494.4(DCST1):​c.37C>G​(p.Gln13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.222

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 (HGNC:):

ACMG classification

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=0.08941993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4	c.37C>G	p.Gln13Glu	missense_variant	2/17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.37C>G	p.Gln13Glu	missense_variant	2/16		NP_001137159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.37C>G	p.Gln13Glu	missense_variant	2/17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000525273.5	n.15C>G		non_coding_transcript_exon_variant	2/15	2		ENSP00000433667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.37C>G (p.Q13E) alteration is located in exon 2 (coding exon 1) of the DCST1 gene. This alteration results from a C to G substitution at nucleotide position 37, causing the glutamine (Q) at amino acid position 13 to be replaced by a glutamic acid (E). 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	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.6
DANN	Benign	0.85
DEOGEN2	Benign	0.019	T;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0050	B;.;.
Vest4		0.058
MutPred		0.10		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.33
MPC		0.13
ClinPred		0.18	T
GERP RS		3.3
Varity_R		0.073
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155006549;