1-12941560-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.293G>T​(p.Trp98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 11)
Exomes 𝑓: 8.1e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PRAMEF6
NM_001010889.2 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14637193).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRAMEF6NM_001010889.2 linkc.293G>T p.Trp98Leu 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.293G>T p.Trp98Leu missense_variant Exon 3 of 4 1 NM_001010889.2 ENSP00000365360.1 Q5VXH4
PRAMEF6ENST00000415464.6 linkc.293G>T p.Trp98Leu missense_variant Exon 3 of 4 1 ENSP00000401281.2 Q5VXH4

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
83442
Hom.:
0
Cov.:
11
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
8.09e-7
AC:
1
AN:
1236736
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
619630
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:
0.0000234
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
83442
Hom.:
0
Cov.:
11
AF XY:
0.00
AC XY:
0
AN XY:
39306
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 24, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.293G>T (p.W98L) alteration is located in exon 3 (coding exon 2) of the PRAMEF6 gene. This alteration results from a G to T substitution at nucleotide position 293, causing the tryptophan (W) at amino acid position 98 to be replaced by a leucine (L). 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
0.26
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.011
N
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-5.6
D;D
REVEL
Benign
0.086
Sift
Uncertain
0.026
D;D
Sift4G
Benign
0.18
T;T
Polyphen
0.19
B;B
Vest4
0.29
MutPred
0.58
Loss of methylation at K99 (P = 0.1247);Loss of methylation at K99 (P = 0.1247);
MVP
0.043
MPC
3.1
ClinPred
0.53
D
GERP RS
0.52
Varity_R
0.14
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-13001390; API