8-104354893-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030788.4(DCSTAMP):c.1046A>G(p.Asp349Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,591,232 control chromosomes in the GnomAD database, including 12,837 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D349E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1133 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11704 hom.)
• Consequence: DCSTAMP NM_030788.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720

Genes affected

DCSTAMP (HGNC:18549): (dendrocyte expressed seven transmembrane protein) This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

DPYS (HGNC:3013): (dihydropyrimidinase) Dihydropyrimidinase catalyzes the conversion of 5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism. Dihydropyrimidinase is expressed at a high level in liver and kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript. Defects in the DPYS gene are linked to dihydropyrimidinuria. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-104354893-A-G is Benign according to our data. Variant chr8-104354893-A-G is described in ClinVar as [Benign]. Clinvar id is 1260089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCSTAMP	NM_030788.4	c.1046A>G	p.Asp349Gly	missense_variant	3/4	ENST00000297581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCSTAMP	ENST00000297581.2	c.1046A>G	p.Asp349Gly	missense_variant	3/4	1	NM_030788.4	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17910 AN: 152158 Hom.: 1129 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.135 AC: 33064 AN: 244382 Hom.: 2441 AF XY: 0.134 AC XY: 17605 AN XY: 131856

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.0814

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.125 AC: 180508 AN: 1438956 Hom.: 11704 Cov.: 31 AF XY: 0.126 AC XY: 90253 AN XY: 715814

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0866

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.118 AC: 17924 AN: 152276 Hom.: 1133 Cov.: 32 AF XY: 0.115 AC XY: 8584 AN XY: 74466

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.147

Alfa AF: 0.131 Hom.: 2549

Bravo AF: 0.122

TwinsUK AF: 0.120 AC: 444

ALSPAC AF: 0.131 AC: 506

ESP6500AA AF: 0.0801 AC: 353

ESP6500EA AF: 0.136 AC: 1169

ExAC AF: 0.133 AC: 16109

Asia WGS AF: 0.153 AC: 531 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

This variant is associated with the following publications: (PMID: 25891874) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.4
Dann	Benign	0.74
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.024
Sift	Benign	0.56	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.039
MPC		0.095
ClinPred		0.000017	T
GERP RS		0.32
Varity_R		0.067
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.32		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3802204; hg19: chr8-105367121; COSMIC: COSV52580331; COSMIC: COSV52580331;