Variant 16-58280450-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001305173.2(PRSS54):c.962C>T(p.Thr321Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PRSS54
NM_001305173.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.59

Variant links:

Genes affected

PRSS54 (HGNC:26336): (serine protease 54) This gene encodes a putative serine-type endopeptidase containing the peptidase S1 domain. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PRSS54 links:

CCDC113 (HGNC:25002): (cilia and flagella associated protein 263) Involved in cilium assembly. Located in centriolar satellite and ciliary basal body. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CCDC113 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04946488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS54	NM_001305173.2 linkuse as main transcript	c.962C>T	p.Thr321Met	missense_variant	7/7	ENST00000567164.6	NP_001292102.1	Q6PEW0A0A140VKC3
CCDC113	NM_014157.4 linkuse as main transcript	c.*673G>A		3_prime_UTR_variant	9/9	ENST00000219299.8	NP_054876.2	Q9H0I3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6 linkuse as main transcript	c.962C>T	p.Thr321Met	missense_variant	7/7	1	NM_001305173.2	ENSP00000455024.1		Q6PEW0
CCDC113	ENST00000219299.8 linkuse as main transcript	c.*673G>A		3_prime_UTR_variant	9/9	1	NM_014157.4	ENSP00000219299.4		Q9H0I3-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.0000151

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 09, 2021

The c.962C>T (p.T321M) alteration is located in exon 7 (coding exon 5) of the PRSS54 gene. This alteration results from a C to T substitution at nucleotide position 962, causing the threonine (T) at amino acid position 321 to be replaced by a methionine (M). 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

0.081

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.14

DANN

Benign

0.59

DEOGEN2

Benign

0.00020

T;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.42

.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

-0.60

N;N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

0.15

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.10

MVP

0.23

MPC

0.15

ClinPred

0.57

GERP RS

-11

Varity_R

0.014

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over