1-12793953-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023013.4(PRAMEF1):ā€‹c.326A>Cā€‹(p.Asp109Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,608,966 control chromosomes in the GnomAD database, including 1 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 1 hom. )

Consequence

PRAMEF1
NM_023013.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.300
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18307966).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRAMEF1NM_023013.4 linkuse as main transcriptc.326A>C p.Asp109Ala missense_variant 3/4 ENST00000332296.7 NP_075389.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRAMEF1ENST00000332296.7 linkuse as main transcriptc.326A>C p.Asp109Ala missense_variant 3/41 NM_023013.4 ENSP00000332134 P1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151248
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000295
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1457718
Hom.:
1
Cov.:
33
AF XY:
0.00000414
AC XY:
3
AN XY:
725100
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151248
Hom.:
0
Cov.:
32
AF XY:
0.0000136
AC XY:
1
AN XY:
73776
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsFeb 16, 2023The c.326A>C (p.D109A) alteration is located in exon 3 (coding exon 2) of the PRAMEF1 gene. This alteration results from a A to C substitution at nucleotide position 326, causing the aspartic acid (D) at amino acid position 109 to be replaced by an alanine (A). 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
0.17
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
6.6
DANN
Benign
0.97
DEOGEN2
Benign
0.010
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.0043
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.066
Sift
Benign
0.11
T
Sift4G
Benign
0.19
T
Polyphen
1.0
D
Vest4
0.14
MVP
0.014
MPC
1.2
ClinPred
0.61
D
GERP RS
-0.80
Varity_R
0.045
gMVP
0.12

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.

Other links and lift over

dbSNP: rs146167299; hg19: chr1-12854102; API