Variant 1-12859726-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_023014.1(PRAMEF2):c.321T>A(p.Asp107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,606,554 control chromosomes in the GnomAD database, including 31 homozygotes. 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 0.00057 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 25 hom. )

Consequence

PRAMEF2
NM_023014.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.388

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021385282).

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF2	NM_023014.1 linkuse as main transcript	c.321T>A	p.Asp107Glu	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.321T>A	p.Asp107Glu	missense_variant	3/4	1	NM_023014.1	ENSP00000240189	P1

Frequencies

GnomAD3 genomes

AF:

0.000570

AC:

AN:

150932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000676

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00237

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000782

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000476

AC:

114

AN:

239450

Hom.:

AF XY:

0.000414

AC XY:

AN XY:

130504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000536

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00119

Gnomad NFE exome

AF:

0.000608

Gnomad OTH exome

AF:

0.000515

GnomAD4 exome

AF:

0.000475

AC:

692

AN:

1455622

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

317

AN XY:

724214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000437

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.000490

Gnomad4 OTH exome

AF:

0.000483

GnomAD4 genome

AF:

0.000570

AC:

AN:

150932

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

AN XY:

73672

show subpopulations

Gnomad4 AFR

AF:

0.0000731

Gnomad4 AMR

AF:

0.0000676

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00237

Gnomad4 NFE

AF:

0.000782

Gnomad4 OTH

AF:

0.00146

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000699

AC:

ExAC

AF:

0.000454

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.000416

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

Feb 09, 2022

The c.321T>A (p.D107E) alteration is located in exon 3 (coding exon 2) of the PRAMEF2 gene. This alteration results from a T to A substitution at nucleotide position 321, causing the aspartic acid (D) at amino acid position 107 to be replaced by a glutamic acid (E). 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

0.21

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.0049

M_CAP

Benign

0.0011

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.9

REVEL

Benign

0.046

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.041

Polyphen

0.51

Vest4

0.063

MutPred

0.39

Loss of helix (P = 0.1299);

MVP

0.040

MPC

0.12

ClinPred

0.044

GERP RS

0.84

Varity_R

0.074

gMVP

0.069

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