6-106105017-G-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. 13/22 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

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 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 id 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 FAILED quality control check.

BS2

High AC in GnomAd4 at 2427 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM1	NM_001198.4 link	c.857G>C	p.Arg286Pro	missense_variant	Exon 5 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.857G>C	p.Arg286Pro	missense_variant	Exon 5 of 7	1	NM_001198.4	ENSP00000358092.4		O75626-1

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

Gnomad4 AFR exome

AF:

0.0497

AC:

1663

AN:

33480

Gnomad4 AMR exome

AF:

0.00700

AC:

313

AN:

44724

Gnomad4 ASJ exome

AF:

0.0267

AC:

699

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39698

Gnomad4 SAS exome

AF:

0.0169

AC:

1462

AN:

86258

Gnomad4 FIN exome

AF:

0.000262

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.00173

AC:

1921

AN:

1112008

Gnomad4 Remaining exome

AF:

0.00892

AC:

539

AN:

60396

Heterozygous variant carriers

481

962

1442

1923

2404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.0456

AC:

0.0455772

AN:

0.0455772

Gnomad4 AMR

AF:

0.0103

AC:

0.0103281

AN:

0.0103281

Gnomad4 ASJ

AF:

0.0277

AC:

0.0276817

AN:

0.0276817

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.0150

AC:

0.0149502

AN:

0.0149502

Gnomad4 FIN

AF:

0.000377

AC:

0.000377287

AN:

0.000377287

Gnomad4 NFE

AF:

0.00244

AC:

0.00244139

AN:

0.00244139

Gnomad4 OTH

AF:

0.0128

AC:

0.0127841

AN:

0.0127841

Heterozygous variant carriers

121

242

363

484

605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Uncertain

0.39

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.18

.;T;.;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.36

T;T;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

.;N;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.060

N;N;.;N;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;T;.;D;T

Sift4G

Benign

0.22

T;T;.;T;T

Polyphen

0.0060

.;B;.;.;.

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)

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