rs149024185

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001198.4(PRDM1):c.811A>G(p.Ile271Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,614,020 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.13

Publications

4 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00558421).

BP6

Variant 6-106104971-A-G is Benign according to our data. Variant chr6-106104971-A-G is described in ClinVar as Benign. ClinVar VariationId is 135078.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 497 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM1	NM_001198.4 link	c.811A>G	p.Ile271Val	missense_variant	Exon 5 of 7	ENST00000369096.9	NP_001189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9 link	c.811A>G	p.Ile271Val	missense_variant	Exon 5 of 7	1	NM_001198.4	ENSP00000358092.4

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

498

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000700

AC:

176

AN:

251490

AF XY:

0.000530

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000270

AC:

395

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00992

AC:

332

AN:

33480

American (AMR)

AF:

0.000313

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.000662

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

102

127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00327

AC:

497

AN:

152130

Hom.:

Cov.:

AF XY:

0.00315

AC XY:

234

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0116

AC:

480

AN:

41504

American (AMR)

AF:

0.000851

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00125

Hom.:

Bravo

AF:

0.00358

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00101

AC:

123

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.20

.;T;.;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.68

T;T;T;T;T

MetaRNN

Benign

0.0056

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M;.;.;.

PhyloP100

2.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.29

N;N;.;N;N

REVEL

Benign

0.17

Sift

Benign

0.48

T;T;.;T;T

Sift4G

Benign

0.73

T;T;.;T;T

Polyphen

0.087

.;B;.;.;.

Vest4

0.14

MVP

0.53

MPC

0.32

ClinPred

0.035

GERP RS

5.6

Varity_R

0.098

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(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