16-31084843-G-A

Variant names:

• chr16-31084843-G-A
• rs7199949
• NM_001039503.3:c.1216C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039503.3(PRSS53):​c.1216C>T​(p.Pro406Ser) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS53 NM_001039503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 41 publications found

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]

ENSG00000255439 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02690646).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039503.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	NM_001039503.3	MANE Select	c.1216C>T	p.Pro406Ser	missense	Exon 8 of 11	NP_001034592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	ENST00000280606.7	TSL:1 MANE Select	c.1216C>T	p.Pro406Ser	missense	Exon 8 of 11	ENSP00000280606.6
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1200C>T		non_coding_transcript_exon	Exon 10 of 13	ENSP00000433035.1
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1200C>T		3_prime_UTR	Exon 10 of 13	ENSP00000433035.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 155268 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1398720 Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0 AN XY: 689776

African (AFR) AF: 0.00 AC: 0 AN: 31836

American (AMR) AF: 0.00 AC: 0 AN: 35908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24826

East Asian (EAS) AF: 0.00 AC: 0 AN: 36036

South Asian (SAS) AF: 0.00 AC: 0 AN: 79010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078796

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.3
DANN	Benign	0.93
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.045	N
PhyloP100		-0.41
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.10
Sift	Benign	0.68	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.37		Loss of stability (P = 0.0863)
MVP		0.14
MPC		0.061
ClinPred		0.046	T
GERP RS		-3.0
Varity_R		0.061
gMVP		0.26

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

Other links and lift over

dbSNP: rs7199949; hg19: chr16-31096164;