dbSNP rs76648802: PRAMEF1:p.Glu110Gly (chr1-12793956-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_023013.4(PRAMEF1):c.329A>G(p.Glu110Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E110D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PRAMEF1
NM_023013.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.177

Publications

14 publications found

Variant links:

Genes affected

PRAMEF1 (HGNC:28840): (PRAME family member 1) This gene is a member of the PRAME (preferentially expressed antigen of melanoma) gene family which is expressed in many cancers but may function in reproductive tissues during development. Alternative promoter usage generates two transcript variants, which encode different isoforms. [provided by RefSeq, Jun 2014]

PRAMEF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0019774735).

BP6

Variant 1-12793956-A-G is Benign according to our data. Variant chr1-12793956-A-G is described in ClinVar as Benign. ClinVar VariationId is 403339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF1	NM_023013.4 link	c.329A>G	p.Glu110Gly	missense_variant	Exon 3 of 4	ENST00000332296.7	NP_075389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAMEF1	ENST00000332296.7 link	c.329A>G	p.Glu110Gly	missense_variant	Exon 3 of 4	1	NM_023013.4	ENSP00000332134.7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.281

AC:

39383

AN:

139918

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.0977

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.243

Hom.:

ExAC

AF:

0.469

AC:

56911

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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: Fails inbreeding coefficient filter -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.9

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.041

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.18

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.047

Sift

Uncertain

0.022

Sift4G

Uncertain

0.041

Polyphen

0.46

Vest4

0.035

MPC

1.2

ClinPred

0.019

GERP RS

0.53

Varity_R

0.058

gMVP

0.11

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over