16-31084843-G-T

Variant names:

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

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>A​(p.Pro406Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (0 hom.)
• 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=0.02965188).

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>A	p.Pro406Thr	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>A	p.Pro406Thr	missense	Exon 8 of 11	ENSP00000280606.6
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1200C>A		non_coding_transcript_exon	Exon 10 of 13	ENSP00000433035.1
	ENSG00000255439	ENST00000533518.5	TSL:1	n.*1200C>A		3_prime_UTR	Exon 10 of 13	ENSP00000433035.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398720 Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0 AN XY: 689776

African (AFR) AF: 0.0000314 AC: 1 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: 9.27e-7 AC: 1 AN: 1078796

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

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 2352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.9
DANN	Benign	0.72
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.41
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.17
Sift	Benign	0.80	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.42		Gain of phosphorylation at P406 (P = 0.0276)
MVP		0.14
MPC		0.067
ClinPred		0.024	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.36

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;