1-155050647-G-A

Variant names:

• chr1-155050647-G-A
• rs756128319
• NM_152494.4:c.1900G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152494.4(DCST1):​c.1900G>A​(p.Gly634Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.167
• Publications: 0 publications found

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)

ADAM15 (HGNC:193): (ADAM metallopeptidase domain 15) The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as a EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101100385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152494.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCST1	NM_152494.4	MANE Select	c.1900G>A	p.Gly634Ser	missense	Exon 17 of 17	NP_689707.2	Q5T197-1
	DCST1	NM_001143687.2		c.1825G>A	p.Gly609Ser	missense	Exon 16 of 16	NP_001137159.1	Q5T197-3
	DCST1-AS1	NR_040772.1		n.519C>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCST1	ENST00000295542.6	TSL:2 MANE Select	c.1900G>A	p.Gly634Ser	missense	Exon 17 of 17	ENSP00000295542.2	Q5T197-1
	DCST1	ENST00000423025.6	TSL:2	c.1825G>A	p.Gly609Ser	missense	Exon 16 of 16	ENSP00000387369.2	Q5T197-3
	DCST1-AS1	ENST00000452962.2	TSL:2	n.526C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000454 AC: 1 AN: 220320 AF XY: 0.00000818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443346 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717322

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.0000227 AC: 1 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39164

South Asian (SAS) AF: 0.00 AC: 0 AN: 85142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106636

Other (OTH) AF: 0.00 AC: 0 AN: 59674

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000841 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.17
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.084
Sift	Benign	0.16	T
Sift4G	Benign	0.33	T
Polyphen		0.031	B
Vest4		0.16
MutPred		0.34		Gain of disorder (P = 0.0455)
MVP		0.081
MPC		0.12
ClinPred		0.19	T
GERP RS		4.1
Varity_R		0.079
gMVP		0.46
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756128319; hg19: chr1-155023123;