chr1-155045940-A-G

Variant names:

• chr1-155045940-A-G
• rs746947901
• NM_152494.4:c.1220A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152494.4(DCST1):​c.1220A>G​(p.Asn407Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. N407I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43
• 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.1220A>G	p.Asn407Ser	missense	Exon 11 of 17	NP_689707.2	Q5T197-1
	DCST1	NM_001143687.2		c.1145A>G	p.Asn382Ser	missense	Exon 10 of 16	NP_001137159.1	Q5T197-3
	DCST1-AS1	NR_040772.1		n.939+20T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCST1	ENST00000295542.6	TSL:2 MANE Select	c.1220A>G	p.Asn407Ser	missense	Exon 11 of 17	ENSP00000295542.2	Q5T197-1
	DCST1	ENST00000368419.2	TSL:1	c.1220A>G	p.Asn407Ser	missense	Exon 10 of 16	ENSP00000357404.2	Q5T197-2
	DCST1	ENST00000525273.5	TSL:2	n.1295A>G		non_coding_transcript_exon	Exon 11 of 15	ENSP00000433667.1	E9PJX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.91		Loss of catalytic residue at N407 (P = 0.0461)
MVP		0.65
MPC		0.50
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.94
gMVP		0.85
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.74		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.74		Position offset: 1

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

Other links and lift over

dbSNP: rs746947901; hg19: chr1-155018416;