rs746947901

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-155045940-A-G
• chr1-155045940-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

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.

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

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4	c.1220A>G	p.Asn407Ser	missense_variant	Exon 11 of 17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.1145A>G	p.Asn382Ser	missense_variant	Exon 10 of 16		NP_001137159.1
DCST1-AS1	NR_040772.1	n.939+20T>C		intron_variant	Intron 3 of 3
DCST1-AS1	NR_040773.1	n.524+20T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.1220A>G	p.Asn407Ser	missense_variant	Exon 11 of 17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000525273.5	n.1295A>G		non_coding_transcript_exon_variant	Exon 11 of 15	2		ENSP00000433667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.94
MutPred		0.91		Loss of catalytic residue at N407 (P = 0.0461);.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs746947901; hg19: chr1-155018416;