Variant chr1-13390558-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001099851.3(PRAMEF17):c.505A>G(p.Arg169Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,452,800 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF17
NM_001099851.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

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=0.12802628).

BP6

Variant 1-13390558-A-G is Benign according to our data. Variant chr1-13390558-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2207433.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF17	NM_001099851.3 linkuse as main transcript	c.505A>G	p.Arg169Gly	missense_variant	2/3	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.505A>G	p.Arg169Gly	missense_variant	2/3	1	NM_001099851.3	ENSP00000365266.3		Q5VTA0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149684

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000267

Gnomad ASJ

AF:

0.00146

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.000866

Gnomad FIN

AF:

0.000480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000749

Gnomad OTH

AF:

0.000490

GnomAD3 exomes

AF:

0.0000551

AC:

AN:

217952

Hom.:

AF XY:

0.0000759

AC XY:

AN XY:

118504

show subpopulations

Gnomad AFR exome

AF:

0.0000731

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000513

Gnomad NFE exome

AF:

0.0000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000249

AC:

362

AN:

1452800

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

174

AN XY:

722830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000806

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000467

AC:

AN:

149794

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

AN XY:

73236

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000267

Gnomad4 ASJ

AF:

0.00146

Gnomad4 EAS

AF:

0.000202

Gnomad4 SAS

AF:

0.000867

Gnomad4 FIN

AF:

0.000480

Gnomad4 NFE

AF:

0.000749

Gnomad4 OTH

AF:

0.000485

Alfa

AF:

0.00127

Hom.:

ExAC

AF:

0.00000837

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2022

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

0.052

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.95

DANN

Benign

0.15

DEOGEN2

Benign

0.044

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.17

M_CAP

Benign

0.00090

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.17

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.0

REVEL

Benign

0.017

Sift

Benign

0.28

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.052

MutPred

0.49

Gain of catalytic residue at C168 (P = 0.0455);

MVP

0.043

MPC

2.2

ClinPred

0.035

GERP RS

-2.2

Varity_R

0.054

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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