chr16-31084173-A-G

Position:

• chr16-31084173-A-G

Variant summary

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

The NM_001039503.3(PRSS53):​c.1588T>C​(p.Phe530Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.75

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 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	Protein	UniProt
PRSS53	NM_001039503.3	c.1588T>C	p.Phe530Leu	missense_variant	10/11	ENST00000280606.7	NP_001034592.1
ZNF646	NM_014699.4	c.*1081A>G		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.1588T>C	p.Phe530Leu	missense_variant	10/11	1	NM_001039503.3	ENSP00000280606	P1
ZNF646	ENST00000300850.5	c.*1081A>G		3_prime_UTR_variant	3/3	1	NM_014699.4	ENSP00000300850	P2
PRSS53	ENST00000486499.1	n.4753T>C		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

Jul 26, 2022

The c.1588T>C (p.F530L) alteration is located in exon 10 (coding exon 10) of the PRSS53 gene. This alteration results from a T to C substitution at nucleotide position 1588, causing the phenylalanine (F) at amino acid position 530 to be replaced by a leucine (L). 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	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.023	D
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.75	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.54	N
REVEL	Uncertain	0.37
Sift	Benign	0.44	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.61
MutPred		0.35		Gain of loop (P = 0.1069);
MVP		0.78
MPC		0.40
ClinPred		0.75	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.40

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: chr16-31095494;