1-155046135-C-G

Variant names:

• chr1-155046135-C-G
• rs919355205
• NM_152494.4:c.1283C>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.1283C>G​(p.Thr428Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000014 (0 hom.)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.561

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-AS1 (HGNC:41147): (DCST1 antisense RNA 1)

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=0.07338622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4	c.1283C>G	p.Thr428Ser	missense_variant	Exon 12 of 17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.1208C>G	p.Thr403Ser	missense_variant	Exon 11 of 16		NP_001137159.1
DCST1-AS1	NR_040772.1	n.764G>C		non_coding_transcript_exon_variant	Exon 3 of 4
DCST1-AS1	NR_040773.1	n.349G>C		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.1283C>G	p.Thr428Ser	missense_variant	Exon 12 of 17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000525273.5	n.1358C>G		non_coding_transcript_exon_variant	Exon 12 of 15	2		ENSP00000433667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1283C>G (p.T428S) alteration is located in exon 12 (coding exon 11) of the DCST1 gene. This alteration results from a C to G substitution at nucleotide position 1283, causing the threonine (T) at amino acid position 428 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.74
DEOGEN2	Benign	0.034	T;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N;.;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.084
Sift	Benign	0.57	T;T;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.013	B;.;.
Vest4		0.18
MutPred		0.64		Gain of disorder (P = 0.0444);.;Gain of disorder (P = 0.0444);
MVP		0.072
MPC		0.11
ClinPred		0.039	T
GERP RS		1.8
Varity_R		0.081
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

Other links and lift over

dbSNP: rs919355205; hg19: chr1-155018611;