Genetic Variant PRAMEF18:p.Arg439His (chr1-13223456-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001099850.2(PRAMEF18):c.1316G>A(p.Arg439His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 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: 2)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF18
NM_001099850.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.349

Variant links:

Genes affected

PRAMEF18 (HGNC:30693): (PRAME family member 18) Predicted to be involved in several processes, including negative regulation of apoptotic process; negative regulation of transcription, DNA-templated; and positive regulation of cell population proliferation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRAMEF18 links:

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=0.19172901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF18	NM_001099850.2 link	c.1316G>A	p.Arg439His	missense_variant	Exon 3 of 3	ENST00000624297.3	NP_001093320.2	Q5VWM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAMEF18	ENST00000624297.3 link	c.1316G>A	p.Arg439His	missense_variant	Exon 3 of 3	1	NM_001099850.2	ENSP00000485473.2		Q5VWM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

26340

Hom.:

Cov.:

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:

0.00000376

AC:

AN:

798558

Hom.:

Cov.:

AF XY:

0.00000488

AC XY:

AN XY:

409930

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:

0.0000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000341

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

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

AF:

0.00

AC:

AN:

26340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

12174

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

Jul 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1316G>A (p.R439H) alteration is located in exon 3 (coding exon 3) of the PRAMEF18 gene. This alteration results from a G to A substitution at nucleotide position 1316, causing the arginine (R) at amino acid position 439 to be replaced by a histidine (H). 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

0.099

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DEOGEN2

Benign

0.011

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.00046

M_CAP

Benign

0.083

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.58

MutPred

0.38

Loss of disorder (P = 0.0538);

MVP

0.014

ClinPred

0.85

GERP RS

-2.7

Varity_R

0.022

gMVP

0.14

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over