rs775219783

Variant names:

• chr1-155046444-G-A
• rs775219783
• NM_152494.4:c.1453G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-155046444-G-A
• chr1-155046444-G-C

Variant summary

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

The NM_152494.4(DCST1):​c.1453G>A​(p.Asp485Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,874 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D485H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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=0.3344692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4	c.1453G>A	p.Asp485Asn	missense_variant	Exon 13 of 17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.1378G>A	p.Asp460Asn	missense_variant	Exon 12 of 16		NP_001137159.1
DCST1-AS1	NR_040772.1	n.653-198C>T		intron_variant	Intron 2 of 3
DCST1-AS1	NR_040773.1	n.329-289C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.1453G>A	p.Asp485Asn	missense_variant	Exon 13 of 17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000368419.2	c.1453G>A	p.Asp485Asn	missense_variant	Exon 12 of 16	1		ENSP00000357404.2
DCST1	ENST00000525273.5	n.1528G>A		non_coding_transcript_exon_variant	Exon 13 of 15	2		ENSP00000433667.1
DCST1	ENST00000423025.6	c.1378G>A	p.Asp460Asn	missense_variant	Exon 12 of 16	2		ENSP00000387369.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251052 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135676

Gnomad AFR exome AF: 0.00

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: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 727240

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.10
Sift	Benign	0.039	D;D;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.60	P;.;.
Vest4		0.39
MutPred		0.72		Loss of catalytic residue at D485 (P = 0.0592);.;Loss of catalytic residue at D485 (P = 0.0592);
MVP		0.42
MPC		0.20
ClinPred		0.58	D
GERP RS		0.90
Varity_R		0.24
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs775219783; hg19: chr1-155018920; COSMIC: COSV55056598; COSMIC: COSV55056598;