Variant chr1-13263101-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001013407.5(PRAMEF5):c.1421G>A(p.Cys474Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00021 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF5
NM_001013407.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.849

Variant links:

Genes affected

PRAMEF5 (HGNC:27995): (PRAME family member 5) 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]

PRAMEF5 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=0.086921215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF5	NM_001013407.5 linkuse as main transcript	c.1421G>A	p.Cys474Tyr	missense_variant	4/4	ENST00000622421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF5	ENST00000622421.3 linkuse as main transcript	c.1421G>A	p.Cys474Tyr	missense_variant	4/4	1	NM_001013407.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

278

AN:

133842

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000477

Gnomad ASJ

AF:

0.000317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000543

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000330

Gnomad OTH

AF:

0.000573

GnomAD3 exomes

AF:

0.000284

AC:

AN:

21094

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

10716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00132

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000251

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000208

AC:

213

AN:

1023552

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

520360

show subpopulations

Gnomad4 AFR exome

AF:

0.00470

Gnomad4 AMR exome

AF:

0.000450

Gnomad4 ASJ exome

AF:

0.0000917

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0000551

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.000469

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00207

AC:

277

AN:

133960

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

140

AN XY:

64624

show subpopulations

Gnomad4 AFR

AF:

0.00680

Gnomad4 AMR

AF:

0.000476

Gnomad4 ASJ

AF:

0.000317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000543

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000330

Gnomad4 OTH

AF:

0.000568

Alfa

AF:

0.00236

Hom.:

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

Aug 12, 2021

The c.1421G>A (p.C474Y) alteration is located in exon 4 (coding exon 3) of the PRAMEF5 gene. This alteration results from a G to A substitution at nucleotide position 1421, causing the cysteine (C) at amino acid position 474 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

0.092

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.4

DANN

Benign

0.33

DEOGEN2

Benign

0.053

Eigen

Benign

-0.80

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0010

M_CAP

Benign

0.00070

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

Sift4G

Benign

0.064

Vest4

0.041

MVP

0.014

ClinPred

0.044

GERP RS

0.36

Varity_R

0.060

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