rs2185379

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

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

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia, autosomal recessive 25
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ATG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRDM1	NM_001198.4 link	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 7	ENST00000369096.9	NP_001189.2	O75626-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9 link	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 7	1	NM_001198.4	ENSP00000358092.4		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

GnomAD2 exomes

AF:

0.0377

AC:

9491

AN:

251492

AF XY:

0.0385

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 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

African (AFR)

AF:

0.0742

AC:

2485

AN:

33478

American (AMR)

AF:

0.0220

AC:

983

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

950

AN:

26136

East Asian (EAS)

AF:

0.0990

AC:

3929

AN:

39700

South Asian (SAS)

AF:

0.0617

AC:

5320

AN:

86258

European-Finnish (FIN)

AF:

0.0218

AC:

1165

AN:

53420

Middle Eastern (MID)

AF:

0.0501

AC:

289

AN:

5768

European-Non Finnish (NFE)

AF:

0.0310

AC:

34425

AN:

1111992

Other (OTH)

AF:

0.0410

AC:

2475

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2855

5710

8566

11421

14276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1394

2788

4182

5576

6970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0452

AC:

6885

AN:

152168

Hom.:

209

Cov.:

AF XY:

0.0449

AC XY:

3340

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0716

AC:

2971

AN:

41474

American (AMR)

AF:

0.0360

AC:

551

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0397

AC:

138

AN:

3472

East Asian (EAS)

AF:

0.0718

AC:

372

AN:

5180

South Asian (SAS)

AF:

0.0570

AC:

275

AN:

4824

European-Finnish (FIN)

AF:

0.0227

AC:

241

AN:

10602

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0315

AC:

2142

AN:

68010

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

319

638

956

1275

1594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0376

Hom.:

589

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

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

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

(source)

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;.;.

PhyloP100

2.8

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over