8-104354995-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_030788.4(DCSTAMP):āc.1148T>Cā(p.Ile383Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,614,168 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 (ā ).
Frequency
Genomes: š 0.000098 ( 0 hom., cov: 32)
Exomes š: 0.000018 ( 0 hom. )
Consequence
DCSTAMP
NM_030788.4 missense
NM_030788.4 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 6.51
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]
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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, 0.763
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCSTAMP | NM_030788.4 | c.1148T>C | p.Ile383Thr | missense_variant | 3/4 | ENST00000297581.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCSTAMP | ENST00000297581.2 | c.1148T>C | p.Ile383Thr | missense_variant | 3/4 | 1 | NM_030788.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251306Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135816
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461830Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727222
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74506
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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 | Feb 15, 2023 | The c.1148T>C (p.I383T) alteration is located in exon 3 (coding exon 2) of the DCSTAMP gene. This alteration results from a T to C substitution at nucleotide position 1148, causing the isoleucine (I) at amino acid position 383 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 2e-04);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at