8-10529524-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_198464.4(PRSS55):c.172A>G(p.Ile58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,842 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00029 ( 2 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 1 hom. )
Consequence
PRSS55
NM_198464.4 missense
NM_198464.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -1.97
Genes affected
PRSS55 (HGNC:30824): (serine protease 55) This gene encodes a member of a group of membrane-anchored chymotrypsin (S1)-like serine proteases. The enocoded protein is primarily expressed in the Leydig and Sertoli cells of the testis and may be involved in male fertility. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.018832147).
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS55 | NM_198464.4 | c.172A>G | p.Ile58Val | missense_variant | 2/5 | ENST00000328655.8 | |
PRSS51 | XR_007060820.1 | n.294+17906T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS55 | ENST00000328655.8 | c.172A>G | p.Ile58Val | missense_variant | 2/5 | 1 | NM_198464.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000290 AC: 44AN: 151972Hom.: 2 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251484Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135916
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461870Hom.: 1 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727234
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GnomAD4 genome ? AF: 0.000290 AC: 44AN: 151972Hom.: 2 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74212
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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 | Oct 03, 2022 | The c.172A>G (p.I58V) alteration is located in exon 2 (coding exon 2) of the PRSS55 gene. This alteration results from a A to G substitution at nucleotide position 172, causing the isoleucine (I) at amino acid position 58 to be replaced by a valine (V). 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
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.1111);Gain of MoRF binding (P = 0.1111);
MVP
MPC
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