rs1564065237

Variant names:

• chr8-104348556-G-C
• rs1564065237
• NM_030788.4:c.4G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-104348556-G-C
• chr8-104348556-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030788.4(DCSTAMP):​c.4G>C​(p.Gly2Arg) 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 benign outcome for this variant. 15/22 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)
• Consequence: DCSTAMP NM_030788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.112
• Publications: 0 publications found

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]

DPYS Gene-Disease associations (from GenCC):

• dihydropyrimidinuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0806008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030788.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCSTAMP	NM_030788.4	MANE Select	c.4G>C	p.Gly2Arg	missense	Exon 2 of 4	NP_110415.1	Q9H295-1
	DCSTAMP	NM_001257317.1		c.4G>C	p.Gly2Arg	missense	Exon 2 of 3	NP_001244246.1	Q9H295-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCSTAMP	ENST00000297581.2	TSL:1 MANE Select	c.4G>C	p.Gly2Arg	missense	Exon 2 of 4	ENSP00000297581.2	Q9H295-1
	DCSTAMP	ENST00000517991.5	TSL:1	c.4G>C	p.Gly2Arg	missense	Exon 1 of 2	ENSP00000428869.1	Q9H295-2
	DCSTAMP	ENST00000622554.1	TSL:5	c.4G>C	p.Gly2Arg	missense	Exon 2 of 3	ENSP00000480546.1	Q9H295-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.3
DANN	Benign	0.94
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.11
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.035
Sift	Benign	0.37	T
Sift4G	Benign	0.23	T
Polyphen		0.044	B
Vest4		0.13
MVP		0.32
MPC		0.094
ClinPred		0.056	T
GERP RS		2.2
PromoterAI		0.14	Neutral
Varity_R		0.041
gMVP		0.15
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1564065237; hg19: chr8-105360784; COSMIC: COSV52576404; COSMIC: COSV52576404;