chr6-106104834-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001198.4(PRDM1):ā€‹c.674A>Gā€‹(p.Gln225Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,460,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

PRDM1
NM_001198.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10223132).
BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRDM1NM_001198.4 linkuse as main transcriptc.674A>G p.Gln225Arg missense_variant 5/7 ENST00000369096.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRDM1ENST00000369096.9 linkuse as main transcriptc.674A>G p.Gln225Arg missense_variant 5/71 NM_001198.4 A1O75626-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249996
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135218
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1460004
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
726458
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2022The c.674A>G (p.Q225R) alteration is located in exon 5 (coding exon 5) of the PRDM1 gene. This alteration results from a A to G substitution at nucleotide position 674, causing the glutamine (Q) at amino acid position 225 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Benign
0.26
.;T;.;.;.
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.79
T;T;T;T;T
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;M;.;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.0
N;N;.;N;N
REVEL
Benign
0.040
Sift
Benign
0.42
T;T;.;T;T
Sift4G
Benign
0.71
T;T;.;T;T
Polyphen
0.11
.;B;.;.;.
Vest4
0.13
MutPred
0.12
.;Gain of loop (P = 0.0435);.;.;.;
MVP
0.68
MPC
0.43
ClinPred
0.40
T
GERP RS
4.6
Varity_R
0.11
gMVP
0.34

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: rs745678262; hg19: chr6-106552709; API