Variant chr1-12861477-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_023014.1(PRAMEF2):c.1123T>C(p.Cys375Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,505,846 control chromosomes in the GnomAD database, including 56,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6694 hom., cov: 30)

Exomes 𝑓: 0.25 ( 49514 hom. )

Consequence

PRAMEF2
NM_023014.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.717

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014611274).

BP6

Variant 1-12861477-T-C is Benign according to our data. Variant chr1-12861477-T-C is described in ClinVar as [Benign]. Clinvar id is 403340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF2	NM_023014.1 linkuse as main transcript	c.1123T>C	p.Cys375Arg	missense_variant	4/4	ENST00000240189.2	NP_075390.1
PRAMEF2	XM_011542004.1 linkuse as main transcript	c.388T>C	p.Cys130Arg	missense_variant	2/2		XP_011540306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF2	ENST00000240189.2 linkuse as main transcript	c.1123T>C	p.Cys375Arg	missense_variant	4/4	1	NM_023014.1	ENSP00000240189	P1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

39689

AN:

137696

Hom.:

6676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.247

AC:

338303

AN:

1368044

Hom.:

49514

Cov.:

AF XY:

0.246

AC XY:

167212

AN XY:

680852

show subpopulations

Gnomad4 AFR exome

AF:

0.399

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.288

AC:

39736

AN:

137802

Hom.:

6694

Cov.:

AF XY:

0.288

AC XY:

19381

AN XY:

67182

show subpopulations

Gnomad4 AFR

AF:

0.397

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.312

Hom.:

1144

ExAC

AF:

0.379

AC:

45951

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.056

DANN

Benign

0.12

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00011

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.2

MutationTaster

Benign

0.89

PrimateAI

Benign

0.42

PROVEAN

Benign

4.0

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.019

MPC

0.063

ClinPred

0.00030

GERP RS

0.82

Varity_R

0.052

gMVP

0.22

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