chr1-155039504-G-C

Position:

• chr1-155039504-G-C

Variant summary

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

The NM_152494.4(DCST1):​c.364G>C​(p.Gly122Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

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]

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, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4	c.364G>C	p.Gly122Arg	missense_variant	5/17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.289G>C	p.Gly97Arg	missense_variant	4/16		NP_001137159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.364G>C	p.Gly122Arg	missense_variant	5/17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000368419.2	c.364G>C	p.Gly122Arg	missense_variant	4/16	1		ENSP00000357404.2
DCST1	ENST00000525273.5	n.439G>C		non_coding_transcript_exon_variant	5/15	2		ENSP00000433667.1
DCST1	ENST00000423025.6	c.289G>C	p.Gly97Arg	missense_variant	4/16	2		ENSP00000387369.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.364G>C (p.G122R) alteration is located in exon 5 (coding exon 4) of the DCST1 gene. This alteration results from a G to C substitution at nucleotide position 364, causing the glycine (G) at amino acid position 122 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M;.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Uncertain	0.33
Sift	Benign	0.062	T;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.86
MutPred		0.85		Gain of methylation at G122 (P = 0.0108);.;Gain of methylation at G122 (P = 0.0108);
MVP		0.76
MPC		0.56
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.29
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155011980;