rs75859409

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001198.4(PRDM1):c.2464C>A(p.Pro822Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,596,132 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.926

Variant links:

Genes affected

PRDM1 (HGNC:9346): (PR/SET domain 1) This gene encodes a protein that acts as a repressor of beta-interferon gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the beta-IFN gene promoter. Transcription of this gene increases upon virus induction. Two alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

PRDM1 links:

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ATG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064637065).

BP6

Variant 6-106107472-C-A is Benign according to our data. Variant chr6-106107472-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 135089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 323 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM1	NM_001198.4 linkuse as main transcript	c.2464C>A	p.Pro822Thr	missense_variant	7/7	ENST00000369096.9	NP_001189.2	O75626-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9 linkuse as main transcript	c.2464C>A	p.Pro822Thr	missense_variant	7/7	1	NM_001198.4	ENSP00000358092.4		O75626-1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.000586

AC:

139

AN:

237156

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

128956

show subpopulations

Gnomad AFR exome

AF:

0.00616

Gnomad AMR exome

AF:

0.000779

Gnomad ASJ exome

AF:

0.000337

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.000716

GnomAD4 exome

AF:

0.000298

AC:

431

AN:

1443938

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

212

AN XY:

717234

show subpopulations

Gnomad4 AFR exome

AF:

0.00622

Gnomad4 AMR exome

AF:

0.000887

Gnomad4 ASJ exome

AF:

0.000676

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000987

Gnomad4 OTH exome

AF:

0.000841

GnomAD4 genome

AF:

0.00212

AC:

323

AN:

152194

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00626

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000441

Hom.:

Bravo

AF:

0.00250

ESP6500AA

AF:

0.00364

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000692

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	PRDM1: BP4 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

.;T;.;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0065

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;M;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.62

N;N;.;N

REVEL

Benign

0.070

Sift

Uncertain

0.016

D;D;.;D

Sift4G

Benign

0.069

T;T;.;T

Polyphen

0.97

.;D;.;.

Vest4

0.091

MVP

0.11

MPC

0.43

ClinPred

0.017

GERP RS

4.0

Varity_R

0.10

gMVP

0.51

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