Variant 8-10532957-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198464.4(PRSS55):c.650T>A(p.Met217Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M217T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRSS55
NM_198464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.190

Variant links:

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]

PRSS55 links:

PRSS51 (HGNC:37321): (serine protease 51) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS51 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS55	NM_198464.4 linkuse as main transcript	c.650T>A	p.Met217Lys	missense_variant	4/5	ENST00000328655.8
PRSS51	XR_007060820.1 linkuse as main transcript	n.294+14473A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS55	ENST00000328655.8 linkuse as main transcript	c.650T>A	p.Met217Lys	missense_variant	4/5	1	NM_198464.4	P1	Q6UWB4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 06, 2023

The c.650T>A (p.M217K) alteration is located in exon 4 (coding exon 4) of the PRSS55 gene. This alteration results from a T to A substitution at nucleotide position 650, causing the methionine (M) at amino acid position 217 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

Cadd

Benign

7.9

Dann

Benign

0.91

DEOGEN2

Benign

0.28

T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.62

T;T

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.80

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.0

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.86

P;.

Vest4

0.37

MutPred

0.84

Loss of catalytic residue at M217 (P = 0.0042);Loss of catalytic residue at M217 (P = 0.0042);

MVP

0.25

MPC

0.0012

ClinPred

0.81

GERP RS

0.28

Varity_R

0.74

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over