14-94442769-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001080451.2(SERPINA11):āc.1106C>Gā(p.Thr369Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
SERPINA11
NM_001080451.2 missense
NM_001080451.2 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 7.12
Genes affected
SERPINA11 (HGNC:19193): (serpin family A member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA11 | NM_001080451.2 | c.1106C>G | p.Thr369Ser | missense_variant | 5/5 | ENST00000334708.4 | |
SERPINA11 | XM_006720105.4 | c.494C>G | p.Thr165Ser | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA11 | ENST00000334708.4 | c.1106C>G | p.Thr369Ser | missense_variant | 5/5 | 1 | NM_001080451.2 | P1 | |
ENST00000536735.1 | n.171+11028G>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247882Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134022
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460342Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726386
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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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 | Sep 06, 2022 | The c.1106C>G (p.T369S) alteration is located in exon 5 (coding exon 4) of the SERPINA11 gene. This alteration results from a C to G substitution at nucleotide position 1106, causing the threonine (T) at amino acid position 369 to be replaced by a serine (S). 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
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K367 (P = 0.0594);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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