7-128945890-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098629.3(IRF5):​c.241G>T​(p.Ala81Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

IRF5
NM_001098629.3 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

Publications

0 publications found
Variant links:
Genes affected
IRF5 (HGNC:6120): (interferon regulatory factor 5) This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]
IRF5 Gene-Disease associations (from GenCC):
  • systemic lupus erythematosus
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF5NM_001098629.3 linkc.241G>T p.Ala81Ser missense_variant Exon 3 of 9 ENST00000357234.10 NP_001092099.1 Q13568-2B7Z1M2C9JAU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF5ENST00000357234.10 linkc.241G>T p.Ala81Ser missense_variant Exon 3 of 9 1 NM_001098629.3 ENSP00000349770.5 Q13568-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 04, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.241G>T (p.A81S) alteration is located in exon 3 (coding exon 2) of the IRF5 gene. This alteration results from a G to T substitution at nucleotide position 241, causing the alanine (A) at amino acid position 81 to be replaced by a serine (S). 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
0.19
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;.;.;.;T;T;D;D;D;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.90
.;D;D;D;D;T;.;D;.;D
M_CAP
Pathogenic
0.38
D
MetaRNN
Uncertain
0.54
D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Benign
1.4
L;.;L;L;.;.;L;L;L;L
PhyloP100
6.7
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.1
N;.;N;N;N;N;N;N;N;.
REVEL
Uncertain
0.54
Sift
Benign
0.078
T;.;D;T;T;T;D;D;D;.
Sift4G
Benign
0.25
T;T;D;T;T;T;D;D;D;T
Polyphen
1.0
D;.;D;.;.;.;D;D;D;.
Vest4
0.18, 0.23, 0.23, 0.24, 0.24, 0.37
MutPred
0.49
Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);Gain of phosphorylation at A81 (P = 0.0771);
MVP
0.92
MPC
1.6
ClinPred
0.92
D
GERP RS
5.1
Varity_R
0.11
gMVP
0.24
Mutation Taster
=55/45
polymorphism

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

Other links and lift over

hg19: chr7-128585944; API