chr16-2853253-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022119.4(PRSS22):​c.794G>A​(p.Gly265Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

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>A	p.Gly265Asp	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>A	p.Gly265Asp	missense	Exon 6 of 6	ENSP00000161006.3	Q9GZN4
	PRSS22	ENST00000576381.2	TSL:1	n.*652G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000458562.2	I3L147
	PRSS22	ENST00000576381.2	TSL:1	n.*652G>A		3_prime_UTR	Exon 6 of 6	ENSP00000458562.2	I3L147

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000880 AC: 2 AN: 227324 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: 0.0000196

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448604 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 721228

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111704

Other (OTH) AF: 0.00 AC: 0 AN: 60264

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Benign	2.0	M
PhyloP100		2.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.84		Loss of catalytic residue at E264 (P = 0.1919)
MVP		0.97
MPC		1.2
ClinPred		0.94	D
GERP RS		4.0
Varity_R		0.79
gMVP		0.96

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;