1-12793414-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_023013.4(PRAMEF1):​c.187T>C​(p.Cys63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,036 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000075 ( 2 hom. )

Consequence

PRAMEF1
NM_023013.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.59
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09754929).
BP6
Variant 1-12793414-T-C is Benign according to our data. Variant chr1-12793414-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3782890.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRAMEF1NM_023013.4 linkc.187T>C p.Cys63Arg missense_variant Exon 2 of 4 ENST00000332296.7 NP_075389.2 O95521B7ZM17

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRAMEF1ENST00000332296.7 linkc.187T>C p.Cys63Arg missense_variant Exon 2 of 4 1 NM_023013.4 ENSP00000332134.7 O95521

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151320
Hom.:
0
Cov.:
31
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000754
AC:
11
AN:
1458716
Hom.:
2
Cov.:
34
AF XY:
0.00000689
AC XY:
5
AN XY:
725562
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:
0.0000187
Gnomad4 NFE exome
AF:
0.00000901
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151320
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73828
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 19, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.031
DANN
Benign
0.14
DEOGEN2
Benign
0.0055
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.00042
N
LIST_S2
Benign
0.036
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.21
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.77
N
REVEL
Benign
0.056
Sift
Benign
0.63
T
Sift4G
Benign
0.61
T
Polyphen
0.0
B
Vest4
0.11
MVP
0.014
MPC
0.64
ClinPred
0.059
T
GERP RS
-2.6
Varity_R
0.11
gMVP
0.26

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: rs1445862560; hg19: chr1-12853563; API