rs753423446

Variant names:

• chr16-2856217-C-T
• rs753423446
• NM_022119.4:c.146G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-2856217-C-T
• chr16-2856217-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022119.4(PRSS22):​c.146G>A​(p.Arg49Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R49W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: PRSS22 NM_022119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58
• Publications: 2 publications found

Genes affected

PRSS22 (HGNC:14368): (serine protease 22) This gene encodes a member of the trypsin family of serine proteases. The enzyme is expressed in the airways in a developmentally regulated manner. The gene is part of a cluster of serine protease genes on chromosome 16. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS22	NM_022119.4	MANE Select	c.146G>A	p.Arg49Gln	missense	Exon 3 of 6	NP_071402.1	Q9GZN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS22	ENST00000161006.8	TSL:1 MANE Select	c.146G>A	p.Arg49Gln	missense	Exon 3 of 6	ENSP00000161006.3	Q9GZN4
	PRSS22	ENST00000576381.2	TSL:1	n.*4G>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000458562.2	I3L147
	PRSS22	ENST00000576381.2	TSL:1	n.*4G>A		3_prime_UTR	Exon 3 of 6	ENSP00000458562.2	I3L147

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152058 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251288 AF XY: 0.0000589

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: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000411 AC: 60 AN: 1461554 Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31 AN XY: 727096

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5592

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111956

Other (OTH) AF: 0.0000331 AC: 2 AN: 60354

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152058 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.67
MVP		0.86
MPC		1.1
ClinPred		0.71	D
GERP RS		4.9
Varity_R		0.69
gMVP		0.93
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs753423446; hg19: chr16-2906218; COSMIC: COSV50723117; COSMIC: COSV50723117;