dbSNP rs199907649: DCST1:p.Pro538Arg (chr1-155047787-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152494.4(DCST1):c.1613C>G(p.Pro538Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. P538L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCST1
NM_152494.4 missense, splice_region

Scores

Splicing: ADA: 0.001210

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

Variant links:

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 links:

DCST1-AS1 (HGNC:41147): (DCST1 antisense RNA 1)

DCST1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35082632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST1	NM_152494.4 link	c.1613C>G	p.Pro538Arg	missense_variant, splice_region_variant	Exon 15 of 17	ENST00000295542.6	NP_689707.2	Q5T197-1B4DXB8B4DXE3
DCST1	NM_001143687.2 link	c.1538C>G	p.Pro513Arg	missense_variant, splice_region_variant	Exon 14 of 16		NP_001137159.1	Q5T197-3B4DXB8B4DXE3
DCST1-AS1	NR_040772.1 link	n.652+1482G>C		intron_variant	Intron 2 of 3
DCST1-AS1	NR_040773.1 link	n.328+1482G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DCST1	ENST00000295542.6 link	c.1613C>G	p.Pro538Arg	missense_variant, splice_region_variant	Exon 15 of 17	2	NM_152494.4	ENSP00000295542.2	Q5T197-1
DCST1	ENST00000368419.2 link	c.1613C>G	p.Pro538Arg	missense_variant, splice_region_variant	Exon 14 of 16	1		ENSP00000357404.2	Q5T197-2
DCST1	ENST00000525273.5 link	n.*108-270C>G		intron_variant	Intron 14 of 14	2		ENSP00000433667.1	E9PJX3
DCST1	ENST00000423025.6 link	c.1538C>G	p.Pro513Arg	missense_variant, splice_region_variant	Exon 14 of 16	2		ENSP00000387369.2	Q5T197-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.019

T;.;.

Eigen

Benign

-0.093

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.27

T;T;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.12

B;.;.

Vest4

0.42

MutPred

0.44

Loss of catalytic residue at P538 (P = 0.0278);.;Loss of catalytic residue at P538 (P = 0.0278);

MVP

0.28

MPC

0.13

ClinPred

0.33

GERP RS

4.4

Varity_R

0.16

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over