Variant 12-7717018-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000345088.3(DPPA3):c.421T>C(p.Trp141Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

DPPA3
ENST00000345088.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

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]

DPPA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
DPPA3	NM_199286.4 linkuse as main transcript	c.421T>C	p.Trp141Arg	missense_variant	4/4	ENST00000345088.3	NP_954980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPPA3	ENST00000345088.3 linkuse as main transcript	c.421T>C	p.Trp141Arg	missense_variant	4/4	1	NM_199286.4	ENSP00000339250	P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251366

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000845

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000984

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.421T>C (p.W141R) alteration is located in exon 4 (coding exon 4) of the DPPA3 gene. This alteration results from a T to C substitution at nucleotide position 421, causing the tryptophan (W) at amino acid position 141 to be replaced by an arginine (R). 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

0.86

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.41

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.31

M_CAP

Benign

0.0085

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.088

Sift

Benign

0.050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.39

MutPred

0.37

Gain of catalytic residue at N139 (P = 0.0345);

MVP

0.51

MPC

0.70

ClinPred

0.59

GERP RS

0.39

Varity_R

0.29

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over