NM_030788.4:c.316G>C

Variant names:

• chr8-104348868-G-C
• rs200594066
• NM_030788.4:c.316G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030788.4(DCSTAMP):​c.316G>C​(p.Val106Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. V106I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCSTAMP NM_030788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

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.316G>C	p.Val106Leu	missense	Exon 2 of 4	NP_110415.1	Q9H295-1
	DCSTAMP	NM_001257317.1		c.316G>C	p.Val106Leu	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.316G>C	p.Val106Leu	missense	Exon 2 of 4	ENSP00000297581.2	Q9H295-1
	DCSTAMP	ENST00000517991.5	TSL:1	c.316G>C	p.Val106Leu	missense	Exon 1 of 2	ENSP00000428869.1	Q9H295-2
	DCSTAMP	ENST00000622554.1	TSL:5	c.316G>C	p.Val106Leu	missense	Exon 2 of 3	ENSP00000480546.1	Q9H295-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0094	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Benign	0.29	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.61	P
Vest4		0.59
MutPred		0.75		Loss of sheet (P = 0.0817)
MVP		0.70
MPC		0.20
ClinPred		0.96	D
GERP RS		5.8
PromoterAI		-0.045	Neutral
Varity_R		0.14
gMVP		0.77
Mutation Taster		=83/17	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: rs200594066; hg19: chr8-105361096;