16-31086145-G-C

Position:

• chr16-31086145-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039503.3(PRSS53):​c.702C>G​(p.Asp234Glu) 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. 15/21 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 NM_001039503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.505

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20002341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS53	NM_001039503.3	c.702C>G	p.Asp234Glu	missense_variant	6/11	ENST00000280606.7	NP_001034592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS53	ENST00000280606.7	c.702C>G	p.Asp234Glu	missense_variant	6/11	1	NM_001039503.3	ENSP00000280606	P1
PRSS53	ENST00000486499.1	n.3484C>G		non_coding_transcript_exon_variant	1/2	2
PRSS53	ENST00000492427.2	n.1652C>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Sep 20, 2023

The c.702C>G (p.D234E) alteration is located in exon 6 (coding exon 6) of the PRSS53 gene. This alteration results from a C to G substitution at nucleotide position 702, causing the aspartic acid (D) at amino acid position 234 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.9
DANN	Benign	0.81
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.82	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.29
Sift	Benign	0.20	T
Sift4G	Uncertain	0.029	D
Polyphen		0.83	P
Vest4		0.16
MutPred		0.64		Gain of loop (P = 0.1069);
MVP		0.19
MPC		0.063
ClinPred		0.28	T
GERP RS		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-31097466;