rs6601483

chr8-10538544-A-Cchr8-10538544-A-Gchr8-10538544-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_198464.4(PRSS55):c.810A>C(p.Ile270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,812 control chromosomes in the GnomAD database, including 335,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (30939 hom., cov: 32)
  • Exomes 𝑓: 0.64 (304969 hom.)
• Consequence: PRSS55 NM_198464.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.551 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS55	NM_198464.4	c.810A>C	p.Ile270=	synonymous_variant	5/5	ENST00000328655.8
PRSS51	XR_007060820.1	n.294+8886T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS55	ENST00000328655.8	c.810A>C	p.Ile270=	synonymous_variant	5/5	1	NM_198464.4	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96621 AN: 151966 Hom.: 30880 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.602

GnomAD3 exomes AF: 0.649 AC: 163036 AN: 251398 Hom.: 53345 AF XY: 0.647 AC XY: 87968 AN XY: 135876

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.695

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.761

Gnomad SAS exome AF: 0.677

Gnomad FIN exome AF: 0.613

Gnomad NFE exome AF: 0.632

Gnomad OTH exome AF: 0.617

GnomAD4 exome AF: 0.645 AC: 942144 AN: 1461728 Hom.: 304969 Cov.: 54 AF XY: 0.644 AC XY: 468282 AN XY: 727176

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.693

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.636 AC: 96744 AN: 152084 Hom.: 30939 Cov.: 32 AF XY: 0.639 AC XY: 47476 AN XY: 74346

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.605

Alfa AF: 0.645 Hom.: 23223

Bravo AF: 0.635

Asia WGS AF: 0.722 AC: 2509 AN: 3478

EpiCase AF: 0.620

EpiControl AF: 0.614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	8.9
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs6601483; hg19: chr8-10396054; COSMIC: COSV60808578;