Variant chr1-13392000-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001099851.3(PRAMEF17):c.923A>G(p.Gln308Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 1,598,128 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 31)

Exomes 𝑓: 0.0093 ( 254 hom. )

Consequence

PRAMEF17
NM_001099851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.15

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066369176).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF17	NM_001099851.3 linkuse as main transcript	c.923A>G	p.Gln308Arg	missense_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.923A>G	p.Gln308Arg	missense_variant	3/3	1	NM_001099851.3	ENSP00000365266.3		Q5VTA0

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1687

AN:

151330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.0799

Gnomad SAS

AF:

0.0125

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.000698

AC:

AN:

103088

Hom.:

AF XY:

0.000686

AC XY:

AN XY:

53932

show subpopulations

Gnomad AFR exome

AF:

0.000349

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00105

Gnomad SAS exome

AF:

0.000904

Gnomad FIN exome

AF:

0.000112

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.000787

GnomAD4 exome

AF:

0.00929

AC:

13434

AN:

1446678

Hom.:

254

Cov.:

AF XY:

0.00951

AC XY:

6849

AN XY:

719902

show subpopulations

Gnomad4 AFR exome

AF:

0.00189

Gnomad4 AMR exome

AF:

0.00842

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.0553

Gnomad4 SAS exome

AF:

0.00976

Gnomad4 FIN exome

AF:

0.00732

Gnomad4 NFE exome

AF:

0.00777

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.0111

AC:

1685

AN:

151450

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

848

AN XY:

74002

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.0144

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.0793

Gnomad4 SAS

AF:

0.0121

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0133

ExAC

AF:

0.00583

AC:

656

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2022

The c.923A>G (p.Q308R) alteration is located in exon 3 (coding exon 3) of the PRAMEF16 gene. This alteration results from a A to G substitution at nucleotide position 923, causing the glutamine (Q) at amino acid position 308 to be replaced by an arginine (R). 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

0.052

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.012

DANN

Benign

0.34

DEOGEN2

Benign

0.014

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.093

MetaRNN

Benign

0.0066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.74

REVEL

Benign

0.050

Sift

Benign

0.091

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.012

MVP

0.043

MPC

1.9

ClinPred

0.0045

GERP RS

-2.1

Varity_R

0.040

gMVP

0.12

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