rs61740099

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-58284658-G-A
• chr16-58284658-G-C

Variant summary

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

The NM_001305173.2(PRSS54):​c.586C>T​(p.Pro196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. P196A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

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

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=0.21861717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.586C>T	p.Pro196Ser	missense_variant	Exon 6 of 7	ENST00000567164.6	NP_001292102.1
PRSS54	NM_001080492.2	c.586C>T	p.Pro196Ser	missense_variant	Exon 6 of 7		NP_001073961.1
PRSS54	NM_001305174.2	c.289C>T	p.Pro97Ser	missense_variant	Exon 5 of 6		NP_001292103.1
PRSS54	XM_047433779.1	c.52C>T	p.Pro18Ser	missense_variant	Exon 2 of 3		XP_047289735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6	c.586C>T	p.Pro196Ser	missense_variant	Exon 6 of 7	1	NM_001305173.2	ENSP00000455024.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.098	T;T;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.53	.;T;T;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.77	N;N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	0.37	T;T;T;.
Polyphen		0.49	P;P;.;.
Vest4		0.17
MutPred		0.28		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;.;
MVP		0.82
MPC		0.52
ClinPred		0.33	T
GERP RS		3.5
Varity_R		0.10
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-58318562;