NM_198464.4:c.742-1091T>G

Variant names:

• chr8-10537385-T-G
• rs7008087
• NM_198464.4:c.742-1091T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198464.4(PRSS55):​c.742-1091T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,982 control chromosomes in the GnomAD database, including 27,866 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 0.60 (27866 hom., cov: 32)
• Consequence: PRSS55 NM_198464.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS55	NM_198464.4	MANE Select	c.742-1091T>G		intron	N/A	NP_940866.2
	PRSS55	NM_001197020.2		c.741+4337T>G		intron	N/A	NP_001183949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS55	ENST00000328655.8	TSL:1 MANE Select	c.742-1091T>G		intron	N/A	ENSP00000333003.3
	PRSS51	ENST00000523024.2	TSL:1	n.-111+10045A>C		intron	N/A	ENSP00000518528.1
	PRSS55	ENST00000522210.1	TSL:2	c.741+4337T>G		intron	N/A	ENSP00000430459.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91746 AN: 151864 Hom.: 27833 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.604 AC: 91833 AN: 151982 Hom.: 27866 Cov.: 32 AF XY: 0.607 AC XY: 45063 AN XY: 74266

African (AFR) AF: 0.577 AC: 23894 AN: 41440

American (AMR) AF: 0.650 AC: 9928 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3468

East Asian (EAS) AF: 0.743 AC: 3845 AN: 5172

South Asian (SAS) AF: 0.663 AC: 3192 AN: 4816

European-Finnish (FIN) AF: 0.581 AC: 6117 AN: 10536

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41261 AN: 67958

Other (OTH) AF: 0.577 AC: 1216 AN: 2106

Alfa AF: 0.583 Hom.: 11606

Bravo AF: 0.602

Asia WGS AF: 0.682 AC: 2370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.51
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

Other links and lift over

dbSNP: rs7008087; hg19: chr8-10394895;