rs2185379

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001198.4(PRDM1):​c.220G>A​(p.Gly74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,614,036 control chromosomes in the GnomAD database, including 1,396 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.045 ( 209 hom., cov: 32)
Exomes 𝑓: 0.036 ( 1187 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

18

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.75
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017325878).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRDM1NM_001198.4 linkuse as main transcriptc.220G>A p.Gly74Ser missense_variant 2/7 ENST00000369096.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRDM1ENST00000369096.9 linkuse as main transcriptc.220G>A p.Gly74Ser missense_variant 2/71 NM_001198.4 A1O75626-1

Frequencies

GnomAD3 genomes
AF:
0.0452
AC:
6869
AN:
152050
Hom.:
206
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0717
Gnomad AMI
AF:
0.0976
Gnomad AMR
AF:
0.0361
Gnomad ASJ
AF:
0.0397
Gnomad EAS
AF:
0.0715
Gnomad SAS
AF:
0.0572
Gnomad FIN
AF:
0.0227
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0315
Gnomad OTH
AF:
0.0398
GnomAD3 exomes
AF:
0.0377
AC:
9491
AN:
251492
Hom.:
245
AF XY:
0.0385
AC XY:
5228
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.0690
Gnomad AMR exome
AF:
0.0193
Gnomad ASJ exome
AF:
0.0368
Gnomad EAS exome
AF:
0.0590
Gnomad SAS exome
AF:
0.0615
Gnomad FIN exome
AF:
0.0235
Gnomad NFE exome
AF:
0.0318
Gnomad OTH exome
AF:
0.0384
GnomAD4 exome
AF:
0.0356
AC:
52021
AN:
1461868
Hom.:
1187
Cov.:
32
AF XY:
0.0365
AC XY:
26562
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0742
Gnomad4 AMR exome
AF:
0.0220
Gnomad4 ASJ exome
AF:
0.0363
Gnomad4 EAS exome
AF:
0.0990
Gnomad4 SAS exome
AF:
0.0617
Gnomad4 FIN exome
AF:
0.0218
Gnomad4 NFE exome
AF:
0.0310
Gnomad4 OTH exome
AF:
0.0410
GnomAD4 genome
AF:
0.0452
AC:
6885
AN:
152168
Hom.:
209
Cov.:
32
AF XY:
0.0449
AC XY:
3340
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0716
Gnomad4 AMR
AF:
0.0360
Gnomad4 ASJ
AF:
0.0397
Gnomad4 EAS
AF:
0.0718
Gnomad4 SAS
AF:
0.0570
Gnomad4 FIN
AF:
0.0227
Gnomad4 NFE
AF:
0.0315
Gnomad4 OTH
AF:
0.0455
Alfa
AF:
0.0361
Hom.:
288
Bravo
AF:
0.0464
TwinsUK
AF:
0.0289
AC:
107
ALSPAC
AF:
0.0311
AC:
120
ESP6500AA
AF:
0.0704
AC:
310
ESP6500EA
AF:
0.0323
AC:
278
ExAC
AF:
0.0396
AC:
4802
Asia WGS
AF:
0.100
AC:
347
AN:
3478
EpiCase
AF:
0.0310
EpiControl
AF:
0.0334

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
20
DANN
Benign
0.63
DEOGEN2
Benign
0.23
.;T;.;.
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.81
T;T;T;T
MetaRNN
Benign
0.0017
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;L;.;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.040
N;N;N;.
REVEL
Benign
0.054
Sift
Benign
0.59
T;T;T;.
Sift4G
Benign
1.0
T;T;T;.
Polyphen
0.016
.;B;.;.
Vest4
0.035
MPC
0.38
ClinPred
0.016
T
GERP RS
4.0
Varity_R
0.052
gMVP
0.60

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.

Other links and lift over

dbSNP: rs2185379; hg19: chr6-106536253; COSMIC: COSV64850169; API