rs754775231

Variant names:

• chr1-155046179-C-G
• rs754775231
• NM_152494.4:c.1327C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-155046179-C-G
• chr1-155046179-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152494.4(DCST1):​c.1327C>G​(p.Pro443Ala) 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. P443S) 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: 5.47

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4	c.1327C>G	p.Pro443Ala	missense_variant	Exon 12 of 17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.1252C>G	p.Pro418Ala	missense_variant	Exon 11 of 16		NP_001137159.1
DCST1-AS1	NR_040772.1	n.720G>C		non_coding_transcript_exon_variant	Exon 3 of 4
DCST1-AS1	NR_040773.1	n.329-24G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.1327C>G	p.Pro443Ala	missense_variant	Exon 12 of 17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000525273.5	n.1402C>G		non_coding_transcript_exon_variant	Exon 12 of 15	2		ENSP00000433667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.022	D;D;D
Sift4G	Benign	0.17	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.75
MutPred		0.53		Gain of ubiquitination at K438 (P = 0.0931);.;Gain of ubiquitination at K438 (P = 0.0931);
MVP		0.45
MPC		0.55
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.62
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs754775231; hg19: chr1-155018655;