chr11-75566404-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001235.5(SERPINH1):c.55G>A(p.Ala19Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,610,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SERPINH1
NM_001235.5 missense
NM_001235.5 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 4.15
Genes affected
SERPINH1 (HGNC:1546): (serpin family H member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The encoded protein is localized to the endoplasmic reticulum and plays a role in collagen biosynthesis as a collagen-specific molecular chaperone. Autoantibodies to the encoded protein have been found in patients with rheumatoid arthritis. Expression of this gene may be a marker for cancer, and nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18966562).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINH1 | NM_001235.5 | c.55G>A | p.Ala19Thr | missense_variant | 2/5 | ENST00000358171.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINH1 | ENST00000358171.8 | c.55G>A | p.Ala19Thr | missense_variant | 2/5 | 1 | NM_001235.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000127 AC: 3AN: 235946Hom.: 0 AF XY: 0.00000769 AC XY: 1AN XY: 130010
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458526Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725486
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74390
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 19 of the SERPINH1 protein (p.Ala19Thr). This variant is present in population databases (rs778730843, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SERPINH1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SERPINH1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;T;T;T;T;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.;.;.;N;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;T;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
P;P;.;.;.;P;.;P;.;.;.;.
Vest4
MutPred
Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);Gain of glycosylation at A19 (P = 0.0318);
MVP
MPC
0.22
ClinPred
T
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