rs193920923

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018189.4(DPPA4):ā€‹c.907T>Cā€‹(p.Trp303Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DPPA4
NM_018189.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.617
Variant links:
Genes affected
DPPA4 (HGNC:19200): (developmental pluripotency associated 4) This gene encodes a nuclear factor that is involved in the maintenance of pluripotency in stem cells and essential for embryogenesis. The encoded protein has a scaffold-attachment factor A/B, acinus and PIAS (SAP) domain that binds DNA and is thought to modify chromatin. Mice with a homozygous knockout of the orthologous gene die during late embryonic development or within hours after birth. Knockout embryos are normal in size at embryonic day 18.5 but exhibit skeletal and lung tissue abnormalities. This gene, when mutated, is highly expressed in embryonal carcinomas, pluripotent germ cell tumors, and other cancers and is thought to play an important role in tumor progression. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1876092).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DPPA4NM_018189.4 linkuse as main transcriptc.907T>C p.Trp303Arg missense_variant 7/7 ENST00000335658.7 NP_060659.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DPPA4ENST00000335658.7 linkuse as main transcriptc.907T>C p.Trp303Arg missense_variant 7/71 NM_018189.4 ENSP00000335306 P1
DPPA4ENST00000463966.5 linkuse as main transcriptn.616T>C non_coding_transcript_exon_variant 6/62
DPPA4ENST00000475135.1 linkuse as main transcriptn.1900T>C non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1394556
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
697738
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:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyScience for Life laboratory, Karolinska Institutet-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.077
Sift
Uncertain
0.0060
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.31
MutPred
0.47
Gain of solvent accessibility (P = 6e-04);
MVP
0.49
MPC
0.46
ClinPred
0.64
D
GERP RS
2.4
Varity_R
0.15
gMVP
0.042

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.

Other links and lift over

dbSNP: rs193920923; hg19: chr3-109046843; COSMIC: COSV59512051; COSMIC: COSV59512051; API