12-7715251-G-C

Position:

• chr12-7715251-G-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPPA3	NM_199286.4	c.151G>C	p.Glu51Gln	missense_variant	2/4	ENST00000345088.3	NP_954980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPPA3	ENST00000345088.3	c.151G>C	p.Glu51Gln	missense_variant	2/4	1	NM_199286.4	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

GnomAD3 exomes AF: 0.276 AC: 69282 AN: 251164 Hom.: 10248 AF XY: 0.275 AC XY: 37364 AN XY: 135740

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 SAS exome AF: 0.221

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

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.276

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

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.240

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 v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2024320; hg19: chr12-7867847; COSMIC: COSV61502945;