8-104349070-T-C

Position:

• chr8-104349070-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030788.4(DCSTAMP):​c.518T>C​(p.Val173Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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: 3.67

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2740009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCSTAMP	NM_030788.4	c.518T>C	p.Val173Ala	missense_variant	2/4	ENST00000297581.2	NP_110415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCSTAMP	ENST00000297581.2	c.518T>C	p.Val173Ala	missense_variant	2/4	1	NM_030788.4	ENSP00000297581	P1
DCSTAMP	ENST00000517991.5	c.518T>C	p.Val173Ala	missense_variant	1/2	1		ENSP00000428869
DCSTAMP	ENST00000622554.1	c.518T>C	p.Val173Ala	missense_variant	2/3	5		ENSP00000480546
DPYS	ENST00000521601.1	n.329-17106A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

May 14, 2024

The c.518T>C (p.V173A) alteration is located in exon 2 (coding exon 1) of the DCSTAMP gene. This alteration results from a T to C substitution at nucleotide position 518, causing the valine (V) at amino acid position 173 to be replaced by an alanine (A). 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	Benign	0.33
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.69	T;T;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M;M;M
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.96	.;N;N
REVEL	Benign	0.17
Sift	Benign	0.045	.;D;D
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		0.92	.;P;.
Vest4		0.24
MutPred		0.52		Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);
MVP		0.49
MPC		0.14
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.081
gMVP		0.62

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: chr8-105361298;