1-155048157-A-G

Variant names:

• chr1-155048157-A-G
• rs769314375
• NM_152494.4:c.1856A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152494.4(DCST1):​c.1856A>G​(p.Gln619Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055651814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4	c.1856A>G	p.Gln619Arg	missense_variant	Exon 16 of 17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.1781A>G	p.Gln594Arg	missense_variant	Exon 15 of 16		NP_001137159.1
DCST1-AS1	NR_040772.1	n.652+1112T>C		intron_variant	Intron 2 of 3
DCST1-AS1	NR_040773.1	n.328+1112T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.1856A>G	p.Gln619Arg	missense_variant	Exon 16 of 17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000368419.2	c.1856A>G	p.Gln619Arg	missense_variant	Exon 15 of 16	1		ENSP00000357404.2
DCST1	ENST00000423025.6	c.1781A>G	p.Gln594Arg	missense_variant	Exon 15 of 16	2		ENSP00000387369.2
DCST1	ENST00000525273.5	n.*208A>G		downstream_gene_variant		2		ENSP00000433667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461698 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1856A>G (p.Q619R) alteration is located in exon 16 (coding exon 15) of the DCST1 gene. This alteration results from a A to G substitution at nucleotide position 1856, causing the glutamine (Q) at amino acid position 619 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	Benign	0.063
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.6
DANN	Benign	0.60
DEOGEN2	Benign	0.017	T;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L;.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.56	N;N;N
REVEL	Benign	0.025
Sift	Benign	0.82	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.14
MutPred		0.28		Gain of MoRF binding (P = 0.0273);.;Gain of MoRF binding (P = 0.0273);
MVP		0.27
MPC		0.13
ClinPred		0.029	T
GERP RS		0.98
Varity_R		0.066
gMVP		0.24

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: rs769314375; hg19: chr1-155020633;