8-10531503-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_198464.4(PRSS55):c.556T>C(p.Trp186Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,794 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 (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
PRSS55
NM_198464.4 missense
NM_198464.4 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 3.65
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.96
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS55 | NM_198464.4 | c.556T>C | p.Trp186Arg | missense_variant | 3/5 | ENST00000328655.8 | |
PRSS51 | XR_007060820.1 | n.294+15927A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS55 | ENST00000328655.8 | c.556T>C | p.Trp186Arg | missense_variant | 3/5 | 1 | NM_198464.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152234Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250372Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135552
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461560Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727080
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152234Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74376
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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 | Aug 14, 2023 | The c.556T>C (p.W186R) alteration is located in exon 3 (coding exon 3) of the PRSS55 gene. This alteration results from a T to C substitution at nucleotide position 556, causing the tryptophan (W) at amino acid position 186 to be replaced by an arginine (R). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Uncertain
D;T
Polyphen
D;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);
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