chr3-109327996-A-G

Variant names:

• chr3-109327996-A-G
• rs193920923
• NM_018189.4:c.907T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.617
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPPA4	ENST00000335658.7	TSL:1 MANE Select	c.907T>C	p.Trp303Arg	missense	Exon 7 of 7	ENSP00000335306.6	Q7L190
	DPPA4	ENST00000936555.1		c.865T>C	p.Trp289Arg	missense	Exon 7 of 7	ENSP00000606614.1
	DPPA4	ENST00000936554.1		c.739T>C	p.Trp247Arg	missense	Exon 7 of 7	ENSP00000606613.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31900

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25702

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.00 AC: 0 AN: 84748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051580

Other (OTH) AF: 0.00 AC: 0 AN: 58118

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.62
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

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