chr6-106105091-A-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001198.4(PRDM1):c.931A>C(p.Lys311Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
PRDM1
NM_001198.4 missense
NM_001198.4 missense
Scores
3
5
9
Clinical Significance
Conservation
PhyloP100: 8.55
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 -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29150546).
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM1 | NM_001198.4 | c.931A>C | p.Lys311Gln | missense_variant | 5/7 | ENST00000369096.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM1 | ENST00000369096.9 | c.931A>C | p.Lys311Gln | missense_variant | 5/7 | 1 | NM_001198.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152016Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251168Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135790
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GnomAD4 exome AF: 0.000135 AC: 197AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.000132 AC XY: 96AN XY: 727244
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GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74246
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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 submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.931A>C (p.K311Q) alteration is located in exon 5 (coding exon 5) of the PRDM1 gene. This alteration results from a A to C substitution at nucleotide position 931, causing the lysine (K) at amino acid position 311 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Uncertain
D;D;.;D
Sift4G
Uncertain
D;T;.;T
Polyphen
1.0
.;D;.;.
Vest4
MVP
MPC
1.2
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at