16-31084143-G-A

Position:

• chr16-31084143-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000280606.7(PRSS53):​c.1618C>T​(p.Pro540Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PRSS53 ENST00000280606.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.43

Genes affected

PRSS53 (HGNC:34407): (serine protease 53) 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]

ZNF646 (HGNC:29004): (zinc finger protein 646) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.028087616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS53	NM_001039503.3	c.1618C>T	p.Pro540Ser	missense_variant	10/11	ENST00000280606.7	NP_001034592.1
ZNF646	NM_014699.4	c.*1051G>A		3_prime_UTR_variant	3/3	ENST00000300850.5	NP_055514.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS53	ENST00000280606.7	c.1618C>T	p.Pro540Ser	missense_variant	10/11	1	NM_001039503.3	ENSP00000280606	P1
ZNF646	ENST00000300850.5	c.*1051G>A		3_prime_UTR_variant	3/3	1	NM_014699.4	ENSP00000300850	P2
PRSS53	ENST00000486499.1	n.4783C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.1618C>T (p.P540S) alteration is located in exon 10 (coding exon 10) of the PRSS53 gene. This alteration results from a C to T substitution at nucleotide position 1618, causing the proline (P) at amino acid position 540 to be replaced by a serine (S). 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	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.037
DANN	Benign	0.68
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.18
Sift	Benign	0.090	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.34		Gain of glycosylation at P540 (P = 0.0453);
MVP		0.14
MPC		0.066
ClinPred		0.11	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.028
gMVP		0.31

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.

Other links and lift over

hg19: chr16-31095464;