11-406935-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001135054.2(SIGIRR):c.787G>T(p.Gly263Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,600,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SIGIRR
NM_001135054.2 missense
NM_001135054.2 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 1.26
Genes affected
SIGIRR (HGNC:30575): (single Ig and TIR domain containing) Predicted to enable NAD+ nucleosidase activity. Involved in negative regulation of DNA-binding transcription factor activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGIRR | NM_001135054.2 | c.787G>T | p.Gly263Cys | missense_variant | 8/10 | ENST00000431843.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGIRR | ENST00000431843.7 | c.787G>T | p.Gly263Cys | missense_variant | 8/10 | 1 | NM_001135054.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000180 AC: 4AN: 222486Hom.: 0 AF XY: 0.0000163 AC XY: 2AN XY: 123076
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GnomAD4 exome AF: 0.00000483 AC: 7AN: 1448742Hom.: 0 Cov.: 33 AF XY: 0.00000416 AC XY: 3AN XY: 720684
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74250
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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 | Nov 05, 2021 | The c.787G>T (p.G263C) alteration is located in exon 8 (coding exon 7) of the SIGIRR gene. This alteration results from a G to T substitution at nucleotide position 787, causing the glycine (G) at amino acid position 263 to be replaced by a cysteine (C). 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
DEOGEN2
Benign
T;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MutPred
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at