chr1-12941141-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001010889.2(PRAMEF6):​c.712G>T​(p.Val238Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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. V238I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 2)

Consequence

PRAMEF6
NM_001010889.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.88
Variant links:
Genes affected
PRAMEF6 (HGNC:30583): (PRAME family member 6) Enables ubiquitin ligase-substrate adaptor activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10060507).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRAMEF6NM_001010889.2 linkc.712G>T p.Val238Phe missense_variant Exon 3 of 4 ENST00000376189.5 NP_001010889.1 Q5VXH4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRAMEF6ENST00000376189.5 linkc.712G>T p.Val238Phe missense_variant Exon 3 of 4 1 NM_001010889.2 ENSP00000365360.1 Q5VXH4
PRAMEF6ENST00000415464.6 linkc.712G>T p.Val238Phe missense_variant Exon 3 of 4 1 ENSP00000401281.2 Q5VXH4

Frequencies

GnomAD3 genomes
Cov.:
2
GnomAD3 exomes
AF:
0.0000196
AC:
1
AN:
51004
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
25654
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000135
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
3
GnomAD4 genome
Cov.:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.042
DANN
Benign
0.31
DEOGEN2
Benign
0.0070
T;T
Eigen
Benign
-2.7
Eigen_PC
Benign
-2.8
FATHMM_MKL
Benign
0.00044
N
M_CAP
Benign
0.00069
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.18
N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.59
N;N
REVEL
Benign
0.059
Sift
Benign
0.63
T;T
Sift4G
Benign
0.64
T;T
Polyphen
0.18
B;B
Vest4
0.099
MutPred
0.38
Loss of catalytic residue at V238 (P = 0.049);Loss of catalytic residue at V238 (P = 0.049);
MVP
0.043
MPC
2.1
ClinPred
0.036
T
GERP RS
-3.1
Varity_R
0.049
gMVP
0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761497343; hg19: chr1-13000971; API