chr11-75566407-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001235.5(SERPINH1):c.58G>A(p.Glu20Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,008 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 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
SERPINH1
NM_001235.5 missense
NM_001235.5 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 2.09
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=0.20288068).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINH1 | NM_001235.5 | c.58G>A | p.Glu20Lys | missense_variant | 2/5 | ENST00000358171.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINH1 | ENST00000358171.8 | c.58G>A | p.Glu20Lys | missense_variant | 2/5 | 1 | NM_001235.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000126 AC: 3AN: 237526Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130726
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458750Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 725628
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74384
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 02, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;T;T;T;T;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
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
Uncertain
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 methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);Gain of methylation at E20 (P = 0.0148);
MVP
MPC
0.26
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