1-155040618-C-A

Position:

• chr1-155040618-C-A

Variant summary

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

The NM_152494.4(DCST1):​c.525C>A​(p.Asp175Glu) 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. 15/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.700

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]

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=0.070118785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4	c.525C>A	p.Asp175Glu	missense_variant	6/17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.450C>A	p.Asp150Glu	missense_variant	5/16		NP_001137159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.525C>A	p.Asp175Glu	missense_variant	6/17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000368419.2	c.525C>A	p.Asp175Glu	missense_variant	5/16	1		ENSP00000357404.2
DCST1	ENST00000525273.5	n.600C>A		non_coding_transcript_exon_variant	6/15	2		ENSP00000433667.1
DCST1	ENST00000423025.6	c.450C>A	p.Asp150Glu	missense_variant	5/16	2		ENSP00000387369.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422280 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703934

Gnomad4 AFR exome AF: 0.00

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.: 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 08, 2022

The c.525C>A (p.D175E) alteration is located in exon 6 (coding exon 5) of the DCST1 gene. This alteration results from a C to A substitution at nucleotide position 525, causing the aspartic acid (D) at amino acid position 175 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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.043	T;.;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.047
Sift	Benign	0.61	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.064	B;.;.
Vest4		0.11
MutPred		0.24		Gain of disorder (P = 0.102);.;Gain of disorder (P = 0.102);
MVP		0.49
MPC		0.12
ClinPred		0.15	T
GERP RS		0.080
Varity_R		0.035
gMVP		0.26

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: chr1-155013094;