chr6-106105221-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001198.4(PRDM1):c.1061G>A(p.Ser354Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,678 control chromosomes in the GnomAD database, including 203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.010 ( 7 hom., cov: 32)

Exomes 𝑓: 0.014 ( 196 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 9.36

Publications

17 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060581267).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0101 (1536/152190) while in subpopulation NFE AF = 0.0168 (1143/68010). AF 95% confidence interval is 0.016. There are 7 homozygotes in GnomAd4. There are 709 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 1536 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM1	NM_001198.4 link	c.1061G>A	p.Ser354Asn	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.1061G>A	p.Ser354Asn	missense_variant	Exon 5 of 7	1	NM_001198.4	ENSP00000358092.4		O75626-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1539

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00989

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0110

AC:

2752

AN:

250466

AF XY:

0.0116

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.00781

Gnomad ASJ exome

AF:

0.00796

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00489

Gnomad NFE exome

AF:

0.0184

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0142

AC:

20813

AN:

1461488

Hom.:

196

Cov.:

AF XY:

0.0139

AC XY:

10141

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.00272

AC:

AN:

33480

American (AMR)

AF:

0.00850

AC:

380

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00723

AC:

189

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00228

AC:

197

AN:

86258

European-Finnish (FIN)

AF:

0.00631

AC:

335

AN:

53068

Middle Eastern (MID)

AF:

0.0251

AC:

145

AN:

5766

European-Non Finnish (NFE)

AF:

0.0168

AC:

18663

AN:

1111980

Other (OTH)

AF:

0.0135

AC:

813

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1424

2848

4271

5695

7119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.0101

AC:

1536

AN:

152190

Hom.:

Cov.:

AF XY:

0.00953

AC XY:

709

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00250

AC:

104

AN:

41524

American (AMR)

AF:

0.00981

AC:

150

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00443

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0168

AC:

1143

AN:

68010

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0110

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0177

AC:

152

ExAC

AF:

0.0109

AC:

1324

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0170

EpiControl

AF:

0.0199

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

0.19

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;D;D

MetaRNN

Benign

0.0061

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M;.;.

PhyloP100

9.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

N;N;.;N

REVEL

Benign

0.10

Sift

Benign

0.11

T;T;.;T

Sift4G

Benign

0.37

T;T;.;T

Polyphen

0.11

.;B;.;.

Vest4

0.11

MPC

0.44

ClinPred

0.087

GERP RS

5.2

Varity_R

0.19

gMVP

0.28

Mutation Taster

=90/10

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