8-104356132-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030788.4(DCSTAMP):c.1347C>A(p.Phe449Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCSTAMP NM_030788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.807

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCSTAMP	NM_030788.4	c.1347C>A	p.Phe449Leu	missense_variant	4/4	ENST00000297581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCSTAMP	ENST00000297581.2	c.1347C>A	p.Phe449Leu	missense_variant	4/4	1	NM_030788.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.1347C>A (p.F449L) alteration is located in exon 4 (coding exon 3) of the DCSTAMP gene. This alteration results from a C to A substitution at nucleotide position 1347, causing the phenylalanine (F) at amino acid position 449 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.0020	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.57
MutPred		0.78		Gain of catalytic residue at F449 (P = 0.0682);
MVP		0.71
MPC		0.39
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.59
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-105368360; COSMIC: COSV52575994;