18-63639761-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002974.4(SERPINB4):āc.485T>Cā(p.Leu162Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,609,956 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 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.0000069 ( 0 hom. )
Consequence
SERPINB4
NM_002974.4 missense
NM_002974.4 missense
Scores
7
5
6
Clinical Significance
Conservation
PhyloP100: 6.17
Genes affected
SERPINB4 (HGNC:10570): (serpin family B member 4) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein is highly expressed in many tumor cells and can inactivate granzyme M, an enzyme that kills tumor cells. This protein, along with serpin B3, can be processed into smaller fragments that aggregate to form an autoantigen in psoriasis, probably by causing chronic inflammation. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.758
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINB4 | NM_002974.4 | c.485T>C | p.Leu162Pro | missense_variant | 6/8 | ENST00000341074.10 | |
SERPINB4 | NM_175041.2 | c.485T>C | p.Leu162Pro | missense_variant | 6/8 | ||
SERPINB4 | XM_011526138.2 | c.485T>C | p.Leu162Pro | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB4 | ENST00000341074.10 | c.485T>C | p.Leu162Pro | missense_variant | 6/8 | 1 | NM_002974.4 | P1 | |
SERPINB4 | ENST00000413673.5 | c.491T>C | p.Leu164Pro | missense_variant | 5/7 | 1 | |||
SERPINB4 | ENST00000436264.1 | c.356T>C | p.Leu119Pro | missense_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000562 AC: 14AN: 249198Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134636
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GnomAD4 exome AF: 0.00000686 AC: 10AN: 1457812Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3AN XY: 725186
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74326
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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 | Apr 07, 2022 | The c.485T>C (p.L162P) alteration is located in exon 6 (coding exon 5) of the SERPINB4 gene. This alteration results from a T to C substitution at nucleotide position 485, causing the leucine (L) at amino acid position 162 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
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