NM_001305173.2:c.586C>G

Variant names:

• chr16-58284658-G-C
• rs61740099
• NM_001305173.2:c.586C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001305173.2(PRSS54):​c.586C>G​(p.Pro196Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,613,930 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0088 (80 hom.)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.80
• Publications: 7 publications found

Genes affected

PRSS54 (HGNC:26336): (serine protease 54) This gene encodes a putative serine-type endopeptidase containing the peptidase S1 domain. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0088810325).
• BP6: Variant 16-58284658-G-C is Benign according to our data. Variant chr16-58284658-G-C is described in ClinVar as Benign. ClinVar VariationId is 710089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305173.2. 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
	PRSS54	NM_001305173.2	MANE Select	c.586C>G	p.Pro196Ala	missense	Exon 6 of 7	NP_001292102.1	Q6PEW0
	PRSS54	NM_001080492.2		c.586C>G	p.Pro196Ala	missense	Exon 6 of 7	NP_001073961.1	Q6PEW0
	PRSS54	NM_001305174.2		c.289C>G	p.Pro97Ala	missense	Exon 5 of 6	NP_001292103.1	F5H6C6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS54	ENST00000567164.6	TSL:1 MANE Select	c.586C>G	p.Pro196Ala	missense	Exon 6 of 7	ENSP00000455024.1	Q6PEW0
	PRSS54	ENST00000219301.8	TSL:5	c.586C>G	p.Pro196Ala	missense	Exon 6 of 7	ENSP00000219301.4	Q6PEW0
	PRSS54	ENST00000543437.5	TSL:2	c.289C>G	p.Pro97Ala	missense	Exon 5 of 6	ENSP00000437705.1	F5H6C6

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 963 AN: 152020 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00408

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.00661

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00741

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00741 AC: 1863 AN: 251482 AF XY: 0.00762

Gnomad AFR exome AF: 0.00449

Gnomad AMR exome AF: 0.00564

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00707

Gnomad NFE exome AF: 0.00817

Gnomad OTH exome AF: 0.00912

GnomAD4 exome AF: 0.00878 AC: 12831 AN: 1461792 Hom.: 80 Cov.: 30 AF XY: 0.00875 AC XY: 6362 AN XY: 727198

African (AFR) AF: 0.00505 AC: 169 AN: 33478

American (AMR) AF: 0.00548 AC: 245 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 264 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0103 AC: 890 AN: 86252

European-Finnish (FIN) AF: 0.00747 AC: 399 AN: 53416

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5766

European-Non Finnish (NFE) AF: 0.00922 AC: 10250 AN: 1111938

Other (OTH) AF: 0.00969 AC: 585 AN: 60386

GnomAD4 genome AF: 0.00633 AC: 963 AN: 152138 Hom.: 4 Cov.: 31 AF XY: 0.00639 AC XY: 475 AN XY: 74386

African (AFR) AF: 0.00405 AC: 168 AN: 41498

American (AMR) AF: 0.00674 AC: 103 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4814

European-Finnish (FIN) AF: 0.00661 AC: 70 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00743 AC: 505 AN: 67994

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00700 Hom.: 2

Bravo AF: 0.00625

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.00455 AC: 20

ESP6500EA AF: 0.00907 AC: 78

ExAC AF: 0.00785 AC: 953

Asia WGS AF: 0.0170 AC: 58 AN: 3478

EpiCase AF: 0.00632

EpiControl AF: 0.00812

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.082
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0089	T
MetaSVM	Uncertain	-0.049	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.8
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Benign	0.14	T
Sift4G	Uncertain	0.060	T
Polyphen		0.93	P
Vest4		0.39
MVP		0.87
MPC		0.60
ClinPred		0.027	T
GERP RS		3.5
Varity_R		0.18
gMVP		0.47
Mutation Taster		=93/7	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

dbSNP: rs61740099; hg19: chr16-58318562;