Variant chr1-13390475-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001099851.3(PRAMEF17):c.422C>T(p.Thr141Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,611,618 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

PRAMEF17
NM_001099851.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.83

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015391231).

BP6

Variant 1-13390475-C-T is Benign according to our data. Variant chr1-13390475-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2465633.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.422C>T	p.Thr141Met	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.422C>T	p.Thr141Met	missense_variant	2/3	1	NM_001099851.3	ENSP00000365266.3		Q5VTA0

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000386

AC:

AN:

41442

Hom.:

AF XY:

0.0000896

AC XY:

AN XY:

22324

show subpopulations

Gnomad AFR exome

AF:

0.000944

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000557

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000273

AC:

398

AN:

1459694

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

726158

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000705

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000244

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000795

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000191

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

This alteration is classified as likely benign based on a combination of the following: 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

0.059

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.020

DANN

Benign

0.077

DEOGEN2

Benign

0.021

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00059

LIST_S2

Benign

0.081

M_CAP

Benign

0.0017

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.65

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

REVEL

Benign

0.0060

Sift

Benign

0.74

Sift4G

Benign

0.39

Polyphen

0.0050

Vest4

0.12

MVP

0.043

MPC

1.9

ClinPred

0.012

GERP RS

-2.2

Varity_R

0.014

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