3-109331927-G-T

Position:

• chr3-109331927-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018189.4(DPPA4):​c.283C>A​(p.His95Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPPA4 NM_018189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPPA4	NM_018189.4	c.283C>A	p.His95Asn	missense_variant	3/7	ENST00000335658.7	NP_060659.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPPA4	ENST00000335658.7	c.283C>A	p.His95Asn	missense_variant	3/7	1	NM_018189.4	ENSP00000335306.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.283C>A (p.H95N) alteration is located in exon 3 (coding exon 3) of the DPPA4 gene. This alteration results from a C to A substitution at nucleotide position 283, causing the histidine (H) at amino acid position 95 to be replaced by an asparagine (N). 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.085
Sift	Benign	0.19	T
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.38		Gain of disorder (P = 0.0773);
MVP		0.65
MPC		0.43
ClinPred		0.45	T
GERP RS		2.0
Varity_R		0.13
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-109050774;