chr1-155046450-A-G

Variant names:

• chr1-155046450-A-G
• NM_152494.4:c.1459A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152494.4(DCST1):​c.1459A>G​(p.Ile487Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000048 (0 hom.)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3726962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4	c.1459A>G	p.Ile487Val	missense_variant	Exon 13 of 17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.1384A>G	p.Ile462Val	missense_variant	Exon 12 of 16		NP_001137159.1
DCST1-AS1	NR_040772.1	n.653-204T>C		intron_variant	Intron 2 of 3
DCST1-AS1	NR_040773.1	n.329-295T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.1459A>G	p.Ile487Val	missense_variant	Exon 13 of 17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000368419.2	c.1459A>G	p.Ile487Val	missense_variant	Exon 12 of 16	1		ENSP00000357404.2
DCST1	ENST00000525273.5	n.1534A>G		non_coding_transcript_exon_variant	Exon 13 of 15	2		ENSP00000433667.1
DCST1	ENST00000423025.6	c.1384A>G	p.Ile462Val	missense_variant	Exon 12 of 16	2		ENSP00000387369.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

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: 0.00000270

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

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1459A>G (p.I487V) alteration is located in exon 13 (coding exon 12) of the DCST1 gene. This alteration results from a A to G substitution at nucleotide position 1459, causing the isoleucine (I) at amino acid position 487 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.97	D;.;.
Vest4		0.22
MutPred		0.72		Gain of phosphorylation at T486 (P = 0.2557);.;Gain of phosphorylation at T486 (P = 0.2557);
MVP		0.32
MPC		0.17
ClinPred		0.74	D
GERP RS		5.0
Varity_R		0.11
gMVP		0.30

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: chr1-155018926;