Genetic Variant NM_023013.4:c.65C>A (chr1-12793292-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023013.4(PRAMEF1):c.65C>A(p.Ala22Asp) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF1
NM_023013.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.754

Publications

3 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14278537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF1	NM_023013.4	MANE Select	c.65C>A	p.Ala22Asp	missense	Exon 2 of 4	NP_075389.2	O95521

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF1	ENST00000332296.7	TSL:1 MANE Select	c.65C>A	p.Ala22Asp	missense	Exon 2 of 4	ENSP00000332134.7	O95521

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000849

AC:

AN:

247494

AF XY:

0.0000970

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000715

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1457052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724744

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39320

South Asian (SAS)

AF:

0.00

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109964

Other (OTH)

AF:

0.00

AC:

AN:

60138

GnomAD4 genome

Cov.:

Alfa

AF:

0.00196

Hom.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.3

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.059

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.035

M_CAP

Benign

0.00081

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-0.75

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.059

Sift

Benign

0.047

Sift4G

Benign

0.12

Polyphen

0.91

Vest4

0.29

MutPred

0.54

Gain of disorder (P = 0.0601)

MVP

0.014

MPC

0.67

ClinPred

0.10

GERP RS

-2.0

Varity_R

0.080

gMVP

0.35

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over