7-141839441-C-T

Position:

• chr7-141839441-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008270.3(PRSS37):​c.73G>A​(p.Asp25Asn) 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. 15/21 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: PRSS37 NM_001008270.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

Genes affected

PRSS37 (HGNC:29211): (serine protease 37) Predicted to enable serine-type endopeptidase activity. Involved in positive regulation of acrosome reaction and regulation of protein processing. Located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2268199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS37	NM_001008270.3	c.73G>A	p.Asp25Asn	missense_variant	2/5	ENST00000350549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS37	ENST00000350549.8	c.73G>A	p.Asp25Asn	missense_variant	2/5	1	NM_001008270.3	P1
PRSS37	ENST00000452758.1	c.41G>A	p.Arg14Lys	missense_variant, NMD_transcript_variant	2/5	1
PRSS37	ENST00000438520.1	c.73G>A	p.Asp25Asn	missense_variant	3/6	5		P1
PRSS37	ENST00000419085.5	c.73G>A	p.Asp25Asn	missense_variant, NMD_transcript_variant	3/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.73G>A (p.D25N) alteration is located in exon 2 (coding exon 2) of the PRSS37 gene. This alteration results from a G to A substitution at nucleotide position 73, causing the aspartic acid (D) at amino acid position 25 to be replaced by an asparagine (N). 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	0.23
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.19
DEOGEN2	Benign	0.00080	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.12	N;N
MutationTaster	Benign	0.56	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.27	B;B
Vest4		0.52
MutPred		0.50		Loss of ubiquitination at K23 (P = 0.1016);Loss of ubiquitination at K23 (P = 0.1016);
MVP		0.28
MPC		0.54
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.17
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-141539241; COSMIC: COSV100633936;