Variant 8-104349177-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_030788.4(DCSTAMP):c.625T>C(p.Ser209Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DCSTAMP
NM_030788.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

Variant links:

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]

DCSTAMP links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCSTAMP	NM_030788.4 linkuse as main transcript	c.625T>C	p.Ser209Pro	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 linkuse as main transcript	c.625T>C	p.Ser209Pro	missense_variant	2/4	1	NM_030788.4	ENSP00000297581	P1	Q9H295-1
DCSTAMP	ENST00000517991.5 linkuse as main transcript	c.625T>C	p.Ser209Pro	missense_variant	1/2	1		ENSP00000428869		Q9H295-2
DCSTAMP	ENST00000622554.1 linkuse as main transcript	c.625T>C	p.Ser209Pro	missense_variant	2/3	5		ENSP00000480546		Q9H295-2
DPYS	ENST00000521601.1 linkuse as main transcript	n.329-17213A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2021

The c.625T>C (p.S209P) 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 625, causing the serine (S) at amino acid position 209 to be replaced by a proline (P). 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

0.20

BayesDel_addAF

Benign

-0.0032

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

.;D;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.69

T;T;.

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.2

.;N;D

REVEL

Benign

0.27

Sift

Uncertain

0.021

.;D;D

Sift4G

Uncertain

0.049

D;T;D

Polyphen

1.0

.;D;.

Vest4

0.65

MutPred

0.57

Loss of ubiquitination at K213 (P = 0.0768);Loss of ubiquitination at K213 (P = 0.0768);Loss of ubiquitination at K213 (P = 0.0768);

MVP

0.66

MPC

0.42

ClinPred

0.95

GERP RS

4.3

Varity_R

0.57

gMVP

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over