1-155040566-C-T

Position:

• chr1-155040566-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152494.4(DCST1):​c.473C>T​(p.Thr158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,590,140 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (34 hom.)
• Consequence: DCST1 NM_152494.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008734852).
• BP6: Variant 1-155040566-C-T is Benign according to our data. Variant chr1-155040566-C-T is described in ClinVar as [Benign]. Clinvar id is 712086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1604/152362) while in subpopulation AFR AF= 0.0362 (1504/41588). AF 95% confidence interval is 0.0346. There are 25 homozygotes in gnomad4. There are 775 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST1	NM_152494.4	c.473C>T	p.Thr158Ile	missense_variant	6/17	ENST00000295542.6	NP_689707.2
DCST1	NM_001143687.2	c.398C>T	p.Thr133Ile	missense_variant	5/16		NP_001137159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCST1	ENST00000295542.6	c.473C>T	p.Thr158Ile	missense_variant	6/17	2	NM_152494.4	ENSP00000295542.2
DCST1	ENST00000368419.2	c.473C>T	p.Thr158Ile	missense_variant	5/16	1		ENSP00000357404.2
DCST1	ENST00000525273.5	n.548C>T		non_coding_transcript_exon_variant	6/15	2		ENSP00000433667.1
DCST1	ENST00000423025.6	c.398C>T	p.Thr133Ile	missense_variant	5/16	2		ENSP00000387369.2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1598 AN: 152244 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00247 AC: 523 AN: 212006 Hom.: 8 AF XY: 0.00185 AC XY: 211 AN XY: 114100

Gnomad AFR exome AF: 0.0357

Gnomad AMR exome AF: 0.00149

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000974

Gnomad OTH exome AF: 0.00111

GnomAD4 exome AF: 0.00106 AC: 1529 AN: 1437778 Hom.: 34 Cov.: 31 AF XY: 0.000950 AC XY: 677 AN XY: 712936

Gnomad4 AFR exome AF: 0.0372

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000157

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000318

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0105 AC: 1604 AN: 152362 Hom.: 25 Cov.: 32 AF XY: 0.0104 AC XY: 775 AN XY: 74516

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00205 Hom.: 4

Bravo AF: 0.0117

ESP6500AA AF: 0.0306 AC: 135

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00262 AC: 317

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T;T;T
MetaRNN	Benign	0.0087	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.97	D;.;.
Vest4		0.74
MVP		0.77
MPC		0.32
ClinPred		0.034	T
GERP RS		4.6
Varity_R		0.29
gMVP		0.76

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: rs9427170; hg19: chr1-155013042;