12-7715251-G-C

Variant names:

• chr12-7715251-G-C
• rs2024320
• NM_199286.4:c.151G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199286.4(DPPA3):​c.151G>C​(p.Glu51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,458 control chromosomes in the GnomAD database, including 76,556 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6084 hom., cov: 31)
  • Exomes 𝑓: 0.31 (70472 hom.)
• Consequence: DPPA3 NM_199286.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.596348E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPPA3	NM_199286.4	MANE Select	c.151G>C	p.Glu51Gln	missense	Exon 2 of 4	NP_954980.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPPA3	ENST00000345088.3	TSL:1 MANE Select	c.151G>C	p.Glu51Gln	missense	Exon 2 of 4	ENSP00000339250.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41651 AN: 151856 Hom.: 6081 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.237

GnomAD2 exomes AF: 0.276 AC: 69282 AN: 251164 AF XY: 0.275

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.305 AC: 445960 AN: 1461484 Hom.: 70472 Cov.: 41 AF XY: 0.303 AC XY: 219979 AN XY: 727050

African (AFR) AF: 0.213 AC: 7135 AN: 33470

American (AMR) AF: 0.234 AC: 10458 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4033 AN: 26128

East Asian (EAS) AF: 0.166 AC: 6570 AN: 39686

South Asian (SAS) AF: 0.222 AC: 19114 AN: 86226

European-Finnish (FIN) AF: 0.409 AC: 21842 AN: 53414

Middle Eastern (MID) AF: 0.135 AC: 777 AN: 5760

European-Non Finnish (NFE) AF: 0.323 AC: 359346 AN: 1111728

Other (OTH) AF: 0.276 AC: 16685 AN: 60370

GnomAD4 genome AF: 0.274 AC: 41675 AN: 151974 Hom.: 6084 Cov.: 31 AF XY: 0.276 AC XY: 20485 AN XY: 74262

African (AFR) AF: 0.212 AC: 8782 AN: 41478

American (AMR) AF: 0.234 AC: 3563 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.184 AC: 950 AN: 5168

South Asian (SAS) AF: 0.215 AC: 1033 AN: 4802

European-Finnish (FIN) AF: 0.405 AC: 4266 AN: 10544

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21700 AN: 67950

Other (OTH) AF: 0.240 AC: 507 AN: 2114

Alfa AF: 0.285 Hom.: 2048

Bravo AF: 0.259

TwinsUK AF: 0.329 AC: 1221

ALSPAC AF: 0.324 AC: 1248

ESP6500AA AF: 0.214 AC: 943

ESP6500EA AF: 0.307 AC: 2638

ExAC AF: 0.277 AC: 33662

Asia WGS AF: 0.219 AC: 760 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.017
DANN	Benign	0.67
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.00096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-2.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.035
Sift	Benign	0.33	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.11
ClinPred		0.0045	T
GERP RS		-5.0
Varity_R		0.047
gMVP		0.034
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2024320; hg19: chr12-7867847; COSMIC: COSV61502945;