8-10525728-G-T

Variant names:

• chr8-10525728-G-T
• rs778395864
• NM_198464.4:c.143G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198464.4(PRSS55):​c.143G>T​(p.Ser48Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,607,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PRSS55 NM_198464.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.555
• Publications: 0 publications found

Genes affected

PRSS55 (HGNC:30824): (serine protease 55) This gene encodes a member of a group of membrane-anchored chymotrypsin (S1)-like serine proteases. The enocoded protein is primarily expressed in the Leydig and Sertoli cells of the testis and may be involved in male fertility. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

PRSS51 (HGNC:37321): (serine protease 51) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042846113).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198464.4. 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
	PRSS55	NM_198464.4	MANE Select	c.143G>T	p.Ser48Ile	missense	Exon 1 of 5	NP_940866.2	Q6UWB4-1
	PRSS55	NM_001197020.2		c.143G>T	p.Ser48Ile	missense	Exon 1 of 5	NP_001183949.1	Q6UWB4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS55	ENST00000328655.8	TSL:1 MANE Select	c.143G>T	p.Ser48Ile	missense	Exon 1 of 5	ENSP00000333003.3	Q6UWB4-1
	PRSS51	ENST00000523024.2	TSL:1	n.-111+21702C>A		intron	N/A	ENSP00000518528.1	A0AA34QVK3
	PRSS55	ENST00000522210.1	TSL:2	c.143G>T	p.Ser48Ile	missense	Exon 1 of 5	ENSP00000430459.1	Q6UWB4-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000340 AC: 8 AN: 235636 AF XY: 0.0000549

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000461

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1454964 Hom.: 0 Cov.: 34 AF XY: 0.00000830 AC XY: 6 AN XY: 723200

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 43616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.000203 AC: 8 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 85190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108966

Other (OTH) AF: 0.00 AC: 0 AN: 60114

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.56
DANN	Benign	0.44
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.56
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.20
Sift	Benign	0.076	T
Sift4G	Uncertain	0.049	D
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.18		Loss of glycosylation at S48 (P = 0.0017)
MVP		0.19
MPC		0.0011
ClinPred		0.019	T
GERP RS		-7.2
PromoterAI		-0.0091	Neutral
Varity_R		0.043
gMVP		0.48
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs778395864; hg19: chr8-10383238;