NM_152494.4:c.1900G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152494.4(DCST1):​c.1900G>C​(p.Gly634Arg) 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. 15/22 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. G634S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04871601).

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>C	p.Gly634Arg	missense	Exon 17 of 17	NP_689707.2	Q5T197-1
	DCST1	NM_001143687.2		c.1825G>C	p.Gly609Arg	missense	Exon 16 of 16	NP_001137159.1	Q5T197-3
	DCST1-AS1	NR_040772.1		n.519C>G		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>C	p.Gly634Arg	missense	Exon 17 of 17	ENSP00000295542.2	Q5T197-1
	DCST1	ENST00000423025.6	TSL:2	c.1825G>C	p.Gly609Arg	missense	Exon 16 of 16	ENSP00000387369.2	Q5T197-3
	DCST1-AS1	ENST00000452962.2	TSL:2	n.526C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000454 AC: 1 AN: 220320 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.0	N
PhyloP100		0.17
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.13
Sift	Benign	0.89	T
Sift4G	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.39		Gain of disorder (P = 0.0184)
MVP		0.12
MPC		0.14
ClinPred		0.16	T
GERP RS		4.1
Varity_R		0.061
gMVP		0.47
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs756128319; hg19: chr1-155023123;