Variant 1-12859763-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_023014.1(PRAMEF2):c.358T>A(p.Trp120Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 430 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF2
NM_023014.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.70

Variant links:

Genes affected

PRAMEF2 (HGNC:28841): (PRAME family member 2) Predicted to be involved in several processes, including negative regulation of apoptotic process; negative regulation of transcription, DNA-templated; and positive regulation of cell population proliferation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRAMEF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060358644).

BP6

Variant 1-12859763-T-A is Benign according to our data. Variant chr1-12859763-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025698.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF2	NM_023014.1 linkuse as main transcript	c.358T>A	p.Trp120Arg	missense_variant	3/4	ENST00000240189.2	NP_075390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF2	ENST00000240189.2 linkuse as main transcript	c.358T>A	p.Trp120Arg	missense_variant	3/4	1	NM_023014.1	ENSP00000240189	P1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1671

AN:

146716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.00841

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0147

GnomAD3 exomes

AF:

0.000518

AC:

128

AN:

246876

Hom.:

AF XY:

0.000539

AC XY:

AN XY:

133548

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.000668

Gnomad SAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000410

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00155

AC:

2195

AN:

1419320

Hom.:

430

Cov.:

AF XY:

0.00176

AC XY:

1238

AN XY:

705062

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00169

Gnomad4 EAS exome

AF:

0.00462

Gnomad4 SAS exome

AF:

0.00591

Gnomad4 FIN exome

AF:

0.000667

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00173

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0114

AC:

1669

AN:

146812

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

834

AN XY:

71646

show subpopulations

Gnomad4 AFR

AF:

0.00277

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.0178

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.00841

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.0146

Alfa

AF:

0.0171

Hom.:

ExAC

AF:

0.00241

AC:

292

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

PRAMEF2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.039

DANN

Benign

0.20

DEOGEN2

Benign

0.0011

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00041

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

2.2

REVEL

Benign

0.052

Sift

Benign

0.82

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.027

MutPred

0.45

Gain of loop (P = 0.0166);

MVP

0.076

MPC

0.063

ClinPred

0.020

GERP RS

-1.7

Varity_R

0.071

gMVP

0.21

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

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