chr11-86807860-A-G

Variant names:

• chr11-86807860-A-G
• NM_007173.6:c.217A>G

Variant summary

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

The NM_007173.6(PRSS23):​c.217A>G​(p.Thr73Ala) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS23 NM_007173.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

Genes affected

PRSS23 (HGNC:14370): (serine protease 23) This gene encodes a conserved member of the trypsin family of serine proteases. Mouse studies found a decrease of mRNA levels of this gene after ovulation was induced. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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=0.029857457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS23	NM_007173.6	c.217A>G	p.Thr73Ala	missense_variant	Exon 2 of 2	ENST00000280258.6	NP_009104.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS23	ENST00000280258.6	c.217A>G	p.Thr73Ala	missense_variant	Exon 2 of 2	1	NM_007173.6	ENSP00000280258.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.217A>G (p.T73A) alteration is located in exon 2 (coding exon 1) of the PRSS23 gene. This alteration results from a A to G substitution at nucleotide position 217, causing the threonine (T) at amino acid position 73 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.9
DANN	Benign	0.67
DEOGEN2	Benign	0.0031	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.030	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.065	.;N
PhyloP100		1.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.051
Sift	Benign	0.43	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.031
MutPred		0.20		Loss of glycosylation at T73 (P = 0.0192);Loss of glycosylation at T73 (P = 0.0192);
MVP		0.088
MPC		0.18
ClinPred		0.056	T
GERP RS		-2.5
Varity_R		0.057
gMVP		0.26
Mutation Taster		=94/6	polymorphism

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

hg19: chr11-86518902; COSMIC: COSV107244415;