NM_001198.4:c.857G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001198.4(PRDM1):c.857G>C(p.Arg286Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00572 in 1,614,046 control chromosomes in the GnomAD database, including 140 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 Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 90 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 3.73

Publications

15 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ATG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022687912).

BP6

Variant 6-106105017-G-C is Benign according to our data. Variant chr6-106105017-G-C is described in ClinVar as Benign. ClinVar VariationId is 135085.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.016 (2427/152158) while in subpopulation AFR AF = 0.0456 (1891/41490). AF 95% confidence interval is 0.0439. There are 50 homozygotes in GnomAd4. There are 1192 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2427 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM1	NM_001198.4	MANE Select	c.857G>C	p.Arg286Pro	missense	Exon 5 of 7	NP_001189.2	O75626-1
	PRDM1	NM_182907.3		c.455G>C	p.Arg152Pro	missense	Exon 3 of 5	NP_878911.1	O75626-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM1	ENST00000369096.9	TSL:1 MANE Select	c.857G>C	p.Arg286Pro	missense	Exon 5 of 7	ENSP00000358092.4	O75626-1
PRDM1	ENST00000369091.6	TSL:1	c.749G>C	p.Arg250Pro	missense	Exon 5 of 7	ENSP00000358087.2	O75626-2
PRDM1	ENST00000369089.3	TSL:1	c.455G>C	p.Arg152Pro	missense	Exon 3 of 5	ENSP00000358085.3	O75626-3

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2429

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00880

AC:

2213

AN:

251452

AF XY:

0.00850

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.0248

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00298

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00466

AC:

6811

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3578

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0497

AC:

1663

AN:

33480

American (AMR)

AF:

0.00700

AC:

313

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0267

AC:

699

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0169

AC:

1462

AN:

86258

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0345

AC:

199

AN:

5768

European-Non Finnish (NFE)

AF:

0.00173

AC:

1921

AN:

1112008

Other (OTH)

AF:

0.00892

AC:

539

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

481

962

1442

1923

2404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<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:

0.0160

AC:

2427

AN:

152158

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1192

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0456

AC:

1891

AN:

41490

American (AMR)

AF:

0.0103

AC:

158

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.0150

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00244

AC:

166

AN:

67994

Other (OTH)

AF:

0.0128

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

121

242

363

484

605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00482

Hom.:

Bravo

AF:

0.0176

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0470

AC:

207

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00932

AC:

1132

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00379

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.18

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

3.7

PrimateAI

Benign

0.31

PROVEAN

Benign

0.060

REVEL

Benign

0.14

Sift

Benign

0.12

Sift4G

Benign

0.22

Polyphen

0.0060

Vest4

0.13

MVP

0.25

MPC

0.56

ClinPred

0.0063

GERP RS

4.4

Varity_R

0.16

gMVP

0.25

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over