Genetic Variant DPPA4:p.Trp303Arg (chr3-109327996-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018189.4(DPPA4):c.907T>C(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. 14/22 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 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DPPA4
NM_018189.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.617

Publications

0 publications found

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]

DPPA4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1876092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPPA4	NM_018189.4	MANE Select	c.907T>C	p.Trp303Arg	missense	Exon 7 of 7	NP_060659.3
DPPA4	NM_001348928.3		c.751T>C	p.Trp251Arg	missense	Exon 7 of 7	NP_001335857.1
DPPA4	NM_001348929.2		c.*62T>C		3_prime_UTR	Exon 6 of 6	NP_001335858.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPPA4	ENST00000335658.7	TSL:1 MANE Select	c.907T>C	p.Trp303Arg	missense	Exon 7 of 7	ENSP00000335306.6
DPPA4	ENST00000463966.5	TSL:2	n.616T>C		non_coding_transcript_exon	Exon 6 of 6
DPPA4	ENST00000475135.1	TSL:2	n.1900T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1394556

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697738

African (AFR)

AF:

0.00

AC:

AN:

31900

American (AMR)

AF:

0.00

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25702

East Asian (EAS)

AF:

0.00

AC:

AN:

39360

South Asian (SAS)

AF:

0.00

AC:

AN:

84748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051580

Other (OTH)

AF:

0.00

AC:

AN:

58118

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.27

M_CAP

Benign

0.0056

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.62

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.21

REVEL

Benign

0.077

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.31

MutPred

0.47

Gain of solvent accessibility (P = 6e-04)

MVP

0.49

MPC

0.46

ClinPred

0.64

GERP RS

2.4

Varity_R

0.15

gMVP

0.042

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over