Variant 6-106088378-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001198.4(PRDM1):c.220G>A(p.Gly74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,614,036 control chromosomes in the GnomAD database, including 1,396 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 not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.045 ( 209 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1187 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.75

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017325878).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM1	NM_001198.4 linkuse as main transcript	c.220G>A	p.Gly74Ser	missense_variant	2/7	ENST00000369096.9	NP_001189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9 linkuse as main transcript	c.220G>A	p.Gly74Ser	missense_variant	2/7	1	NM_001198.4	ENSP00000358092	A1	O75626-1

Frequencies

GnomAD3 genomes

AF:

0.0452

AC:

6869

AN:

152050

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0717

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.0715

Gnomad SAS

AF:

0.0572

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0315

Gnomad OTH

AF:

0.0398

GnomAD3 exomes

AF:

0.0377

AC:

9491

AN:

251492

Hom.:

245

AF XY:

0.0385

AC XY:

5228

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0690

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.0590

Gnomad SAS exome

AF:

0.0615

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0318

Gnomad OTH exome

AF:

0.0384

GnomAD4 exome

AF:

0.0356

AC:

52021

AN:

1461868

Hom.:

1187

Cov.:

AF XY:

0.0365

AC XY:

26562

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0742

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.0990

Gnomad4 SAS exome

AF:

0.0617

Gnomad4 FIN exome

AF:

0.0218

Gnomad4 NFE exome

AF:

0.0310

Gnomad4 OTH exome

AF:

0.0410

GnomAD4 genome

AF:

0.0452

AC:

6885

AN:

152168

Hom.:

209

Cov.:

AF XY:

0.0449

AC XY:

3340

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0716

Gnomad4 AMR

AF:

0.0360

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.0718

Gnomad4 SAS

AF:

0.0570

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.0315

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0361

Hom.:

288

Bravo

AF:

0.0464

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0311

AC:

120

ESP6500AA

AF:

0.0704

AC:

310

ESP6500EA

AF:

0.0323

AC:

278

ExAC

AF:

0.0396

AC:

4802

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.0310

EpiControl

AF:

0.0334

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

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

0.12

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.23

.;T;.;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.040

N;N;N;.

REVEL

Benign

0.054

Sift

Benign

0.59

T;T;T;.

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.016

.;B;.;.

Vest4

0.035

MPC

0.38

ClinPred

0.016

GERP RS

4.0

Varity_R

0.052

gMVP

0.60

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