NM_001198.4:c.1222G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001198.4(PRDM1):c.1222G>C(p.Ala408Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,613,926 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.568

Publications

13 publications found

Variant links:

COSMIC-nc: COSV104426916

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011618227).

BS2

High AC in GnomAd4 at 95 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.1222G>C	p.Ala408Pro	missense	Exon 5 of 7	NP_001189.2	O75626-1
	PRDM1	NM_182907.3		c.820G>C	p.Ala274Pro	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.1222G>C	p.Ala408Pro	missense	Exon 5 of 7	ENSP00000358092.4	O75626-1
PRDM1	ENST00000369091.6	TSL:1	c.1114G>C	p.Ala372Pro	missense	Exon 5 of 7	ENSP00000358087.2	O75626-2
PRDM1	ENST00000369089.3	TSL:1	c.820G>C	p.Ala274Pro	missense	Exon 3 of 5	ENSP00000358085.3	O75626-3

Frequencies

GnomAD3 genomes

AF:

0.000625

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000573

AC:

144

AN:

251242

AF XY:

0.000618

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000547

AC:

799

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000554

AC XY:

403

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.000425

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00149

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000672

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000538

AC:

598

AN:

1112000

Other (OTH)

AF:

0.000745

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

125

188

250

313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000625

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.000754

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41472

American (AMR)

AF:

0.00144

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00208

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

67988

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

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:

0.000690

Hom.:

Bravo

AF:

0.000638

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000626

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.79

M_CAP

Benign

0.011

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

0.57

PrimateAI

Benign

0.42

PROVEAN

Benign

0.68

REVEL

Benign

0.039

Sift

Benign

0.36

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.13

MVP

0.12

MPC

0.50

ClinPred

0.0080

GERP RS

2.4

Varity_R

0.091

gMVP

0.45

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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