Variant chr1-12920180-C-T 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_001012277.5(PRAMEF7):c.1192C>T(p.Arg398Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRAMEF7
NM_001012277.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.477

Variant links:

Genes affected

PRAMEF7 (HGNC:28415): (PRAME family member 7) 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]

PRAMEF7 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=0.020742744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF7	NM_001012277.5 linkuse as main transcript	c.1192C>T	p.Arg398Cys	missense_variant	4/4	ENST00000697200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF7	ENST00000697200.1 linkuse as main transcript	c.1192C>T	p.Arg398Cys	missense_variant	4/4		NM_001012277.5	P1
PRAMEF7	ENST00000330881.6 linkuse as main transcript	c.1192C>T	p.Arg398Cys	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

117

AN:

148370

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00128

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000957

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000989

GnomAD3 exomes

AF:

0.000405

AC:

AN:

44400

Hom.:

AF XY:

0.000536

AC XY:

AN XY:

22394

show subpopulations

Gnomad AFR exome

AF:

0.00312

Gnomad AMR exome

AF:

0.000254

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000108

AC:

157

AN:

1459674

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

726186

show subpopulations

Gnomad4 AFR exome

AF:

0.00258

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000802

AC:

119

AN:

148468

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

AN XY:

72410

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00128

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000202

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000957

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00196

Alfa

AF:

0.000843

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

Oct 03, 2022

The c.1192C>T (p.R398C) alteration is located in exon 3 (coding exon 3) of the PRAMEF7 gene. This alteration results from a C to T substitution at nucleotide position 1192, causing the arginine (R) at amino acid position 398 to be replaced by a cysteine (C). 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

0.086

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.7

DANN

Benign

0.89

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0094

M_CAP

Benign

0.0081

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.020

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

Sift4G

Benign

0.30

T;T

Polyphen

0.0060

B;B

Vest4

0.079

MVP

0.40

ClinPred

0.0078

GERP RS

-0.55

Varity_R

0.057

gMVP

0.18

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