Variant 1-12859056-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_023014.1(PRAMEF2):c.47G>C(p.Ser16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000511 in 1,604,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PRAMEF2
NM_023014.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.483

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041906267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF2	NM_023014.1 linkuse as main transcript	c.47G>C	p.Ser16Thr	missense_variant	2/4	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.47G>C	p.Ser16Thr	missense_variant	2/4	1	NM_023014.1	ENSP00000240189	P1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

148922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000698

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000641

AC:

AN:

249586

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.000931

Gnomad AMR exome

AF:

0.0000297

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1454984

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

723814

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.0000460

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.000289

AC:

AN:

149026

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

72652

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.0000698

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000711

Hom.:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000907

AC:

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

May 05, 2023

The c.47G>C (p.S16T) alteration is located in exon 2 (coding exon 1) of the PRAMEF2 gene. This alteration results from a G to C substitution at nucleotide position 47, causing the serine (S) at amino acid position 16 to be replaced by a threonine (T). 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

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.011

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.012

M_CAP

Benign

0.0020

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.035

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.98

Vest4

0.13

MVP

0.014

MPC

0.29

ClinPred

0.083

GERP RS

0.84

Varity_R

0.14

gMVP

0.25

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