Variant 1-12859760-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_023014.1(PRAMEF2):c.355G>T(p.Ala119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 146,902 control chromosomes in the GnomAD database, including 19 homozygotes. 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 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 402 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF2
NM_023014.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.94

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036302805).

BP6

Variant 1-12859760-G-T is Benign according to our data. Variant chr1-12859760-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025685.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0115 (1691/146902) while in subpopulation SAS AF= 0.0262 (118/4496). AF 95% confidence interval is 0.0224. There are 19 homozygotes in gnomad4. There are 852 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF2	NM_023014.1 linkuse as main transcript	c.355G>T	p.Ala119Ser	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.355G>T	p.Ala119Ser	missense_variant	3/4	1	NM_023014.1	ENSP00000240189	P1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1692

AN:

146804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.0184

Gnomad SAS

AF:

0.0264

Gnomad FIN

AF:

0.00841

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0142

GnomAD3 exomes

AF:

0.000575

AC:

142

AN:

246996

Hom.:

AF XY:

0.000591

AC XY:

AN XY:

133654

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000958

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.000779

Gnomad SAS exome

AF:

0.00107

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000464

Gnomad OTH exome

AF:

0.000832

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00149

AC:

2123

AN:

1420766

Hom.:

402

Cov.:

AF XY:

0.00171

AC XY:

1209

AN XY:

705798

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.00468

Gnomad4 SAS exome

AF:

0.00586

Gnomad4 FIN exome

AF:

0.000762

Gnomad4 NFE exome

AF:

0.00107

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.0115

AC:

1691

AN:

146902

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

852

AN XY:

71716

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.0152

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.0184

Gnomad4 SAS

AF:

0.0262

Gnomad4 FIN

AF:

0.00841

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0146

Alfa

AF:

0.0168

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: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.048

DANN

Benign

0.67

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00052

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.81

REVEL

Benign

0.017

Sift

Benign

0.40

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.051

MVP

0.048

MPC

0.040

ClinPred

0.0066

GERP RS

-1.7

Varity_R

0.048

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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