16-2853253-C-G

Variant names:

• chr16-2853253-C-G
• rs776959250
• NM_022119.4:c.794G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022119.4(PRSS22):​c.794G>C​(p.Gly265Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G265V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS22 NM_022119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.794G>C	p.Gly265Ala	missense	Exon 6 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.794G>C	p.Gly265Ala	missense	Exon 6 of 6	ENSP00000161006.3	Q9GZN4
	PRSS22	ENST00000576381.2	TSL:1	n.*652G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000458562.2	I3L147
	PRSS22	ENST00000576381.2	TSL:1	n.*652G>C		3_prime_UTR	Exon 6 of 6	ENSP00000458562.2	I3L147

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.79
Sift	Benign	0.054	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.21
MutPred		0.86		Loss of disorder (P = 0.2561)
MVP		0.96
MPC		1.1
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.47
gMVP		0.93

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: rs776959250; hg19: chr16-2903254;