rs705837

Positions:

• chr4-118304785-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000296498.3(PRSS12):​c.1631+3651G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,724 control chromosomes in the GnomAD database, including 8,012 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 0.29 (8012 hom., cov: 32)
• Consequence: PRSS12 ENST00000296498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

Genes affected

PRSS12 (HGNC:9477): (serine protease 12) This gene encodes a member of the trypsin family of serine proteases and contains a signal peptide, a proline-rich region, a Kringle domain, four scavenger receptor cysteine-rich domains, and a trypsin-like serine protease domain. The protein, sometimes referred to as neurotrypsin or motopsin, is secreted from neuronal cells and localizes to the synaptic cleft. Studies in mice show that this protein cleaves a protein, agrin, that is important for the formation and maintenance of exitatory synapses. Defects in this gene cause a form of autosomal recessive cognitive impairment (MRT1). [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS12	NM_003619.4	c.1631+3651G>A		intron_variant		ENST00000296498.3	NP_003610.2
PRSS12	XM_005263318.5	c.*23-906G>A		intron_variant			XP_005263375.1
PRSS12	XM_011532387.3	c.1632-906G>A		intron_variant			XP_011530689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3	c.1631+3651G>A		intron_variant		1	NM_003619.4	ENSP00000296498	P1
PRSS12	ENST00000515089.1	n.278-906G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43746 AN: 151604 Hom.: 8016 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.288 AC: 43741 AN: 151724 Hom.: 8012 Cov.: 32 AF XY: 0.285 AC XY: 21154 AN XY: 74140

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.311

Alfa AF: 0.366 Hom.: 4177

Bravo AF: 0.282

Asia WGS AF: 0.233 AC: 813 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.3
DANN	Benign	0.74

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: rs705837; hg19: chr4-119225940;