12-7717037-C-G

Variant names:

• chr12-7717037-C-G
• rs752855109
• NM_199286.4:c.440C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199286.4(DPPA3):​c.440C>G​(p.Ala147Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A147V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPPA3 NM_199286.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 0 publications found

Genes affected

DPPA3 (HGNC:19199): (developmental pluripotency associated 3) This gene encodes a protein that in mice may function as a maternal factor during the preimplantation stage of development. In mice, this gene may play a role in transcriptional repression, cell division, and maintenance of cell pluripotentiality. In humans, related intronless loci are located on chromosomes 14 and X. [provided by RefSeq, Jul 2008]

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=0.17452884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199286.4. 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
	DPPA3	NM_199286.4	MANE Select	c.440C>G	p.Ala147Gly	missense	Exon 4 of 4	NP_954980.1	Q6W0C5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPPA3	ENST00000345088.3	TSL:1 MANE Select	c.440C>G	p.Ala147Gly	missense	Exon 4 of 4	ENSP00000339250.2	Q6W0C5
	DPPA3	ENST00000934351.1		c.437C>G	p.Ala146Gly	missense	Exon 4 of 4	ENSP00000604410.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.91
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.063
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.15
MVP		0.24
MPC		0.50
ClinPred		0.57	D
GERP RS		-0.63
Varity_R		0.11
gMVP		0.012
Mutation Taster		=100/0	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: rs752855109; hg19: chr12-7869633;