Variant chr1-12859754-C-T 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.349C>T(p.Pro117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P117R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 371 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF2
NM_023014.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.26

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=0.0050005913).

BP6

Variant 1-12859754-C-T is Benign according to our data. Variant chr1-12859754-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025679.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1 linkuse as main transcript	c.349C>T	p.Pro117Ser	missense_variant	3/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2 linkuse as main transcript	c.349C>T	p.Pro117Ser	missense_variant	3/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1794

AN:

146886

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00324

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.00851

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0147

GnomAD3 exomes

AF:

0.000645

AC:

159

AN:

246442

Hom.:

AF XY:

0.000615

AC XY:

AN XY:

133388

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.000503

Gnomad EAS exome

AF:

0.00100

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000527

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00155

AC:

2206

AN:

1422516

Hom.:

371

Cov.:

AF XY:

0.00176

AC XY:

1246

AN XY:

706606

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.00274

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00481

Gnomad4 SAS exome

AF:

0.00613

Gnomad4 FIN exome

AF:

0.000630

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0122

AC:

1792

AN:

146982

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

893

AN XY:

71724

show subpopulations

Gnomad4 AFR

AF:

0.00323

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.00851

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.0145

Alfa

AF:

0.0169

Hom.:

ExAC

AF:

0.00243

AC:

295

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

0.097

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0040

DANN

Benign

0.060

DEOGEN2

Benign

0.00086

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00029

M_CAP

Benign

0.00098

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

3.4

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.039

MVP

0.072

MPC

0.042

ClinPred

0.021

GERP RS

-1.7

Varity_R

0.016

gMVP

0.12

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