chr8-10538544-A-C

Variant names:

• chr8-10538544-A-C
• rs6601483
• NM_198464.4:c.810A>C
• PRSS55 p.Ile270Ile

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_198464.4(PRSS55):​c.810A>C​(p.Ile270Ile) 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
• Publications: 19 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: Benign. The variant received -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.

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.810A>C	p.Ile270Ile	synonymous	Exon 5 of 5	NP_940866.2	Q6UWB4-1
	PRSS55	NM_001197020.2		c.741+5496A>C		intron	N/A	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.810A>C	p.Ile270Ile	synonymous	Exon 5 of 5	ENSP00000333003.3	Q6UWB4-1
	PRSS51	ENST00000523024.2	TSL:1	n.-111+8886T>G		intron	N/A	ENSP00000518528.1	A0AA34QVK3
	PRSS55	ENST00000522210.1	TSL:2	c.741+5496A>C		intron	N/A	ENSP00000430459.1	Q6UWB4-2

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

GnomAD2 exomes AF: 0.649 AC: 163036 AN: 251398 AF XY: 0.647

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 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

African (AFR) AF: 0.610 AC: 20432 AN: 33480

American (AMR) AF: 0.693 AC: 30992 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 13628 AN: 26136

East Asian (EAS) AF: 0.785 AC: 31178 AN: 39700

South Asian (SAS) AF: 0.679 AC: 58521 AN: 86250

European-Finnish (FIN) AF: 0.618 AC: 32987 AN: 53418

Middle Eastern (MID) AF: 0.570 AC: 3279 AN: 5748

European-Non Finnish (NFE) AF: 0.641 AC: 712524 AN: 1111888

Other (OTH) AF: 0.639 AC: 38603 AN: 60386

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

African (AFR) AF: 0.615 AC: 25489 AN: 41478

American (AMR) AF: 0.691 AC: 10564 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3470

East Asian (EAS) AF: 0.769 AC: 3967 AN: 5160

South Asian (SAS) AF: 0.693 AC: 3345 AN: 4824

European-Finnish (FIN) AF: 0.622 AC: 6574 AN: 10570

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43266 AN: 67978

Other (OTH) AF: 0.605 AC: 1278 AN: 2114

Alfa AF: 0.650 Hom.: 33729

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.9
DANN	Benign	0.81
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6601483;

hg19: chr8-10396054;

COSMIC: COSV60808578;