Variant chr1-13391946-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099851.3(PRAMEF17):c.869G>A(p.Cys290Tyr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 151,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF17
NM_001099851.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.269

Variant links:

Genes affected

PRAMEF17 (HGNC:29485): (PRAME family member 17) 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]

PRAMEF17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034348756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF17	NM_001099851.3 linkuse as main transcript	c.869G>A	p.Cys290Tyr	missense_variant, splice_region_variant	3/3	ENST00000376098.4	NP_001093321.1	Q5VTA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF17	ENST00000376098.4 linkuse as main transcript	c.869G>A	p.Cys290Tyr	missense_variant, splice_region_variant	3/3	1	NM_001099851.3	ENSP00000365266.3		Q5VTA0

Frequencies

GnomAD3 genomes

AF:

0.000521

AC:

AN:

151756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000779

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000736

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0726

AC:

6177

AN:

85026

Hom.:

203

AF XY:

0.0750

AC XY:

3339

AN XY:

44520

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0354

Gnomad EAS exome

AF:

0.0752

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.0926

Gnomad OTH exome

AF:

0.0547

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00229

AC:

3253

AN:

1422268

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1602

AN XY:

708394

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.0000773

Gnomad4 EAS exome

AF:

0.00448

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.000471

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.000540

AC:

AN:

151872

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000780

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000736

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00199

Hom.:

ExAC

AF:

0.000270

AC:

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 submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.869G>A (p.C290Y) alteration is located in exon 3 (coding exon 3) of the PRAMEF17 gene. This alteration results from a G to A substitution at nucleotide position 869, causing the cysteine (C) at amino acid position 290 to be replaced by a tyrosine (Y). 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

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.20

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.51

M_CAP

Benign

0.0034

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-8.7

REVEL

Benign

0.11

Sift

Benign

0.036

Sift4G

Benign

0.11

Polyphen

0.022

Vest4

0.11

MVP

0.043

MPC

2.6

ClinPred

0.033

GERP RS

-2.1

Varity_R

0.23

gMVP

0.25

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.

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