rs705837

Variant names:

• chr4-118304785-C-T
• rs705837
• NM_003619.4:c.1631+3651G>A

Variant summary

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

The NM_003619.4(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 NM_003619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 6 publications found

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]

PRSS12 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 1

  Inheritance: Unknown, AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003619.4. 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
	PRSS12	NM_003619.4	MANE Select	c.1631+3651G>A		intron	N/A	NP_003610.2	P56730
	PRSS12	NM_001440549.1		c.1631+3651G>A		intron	N/A	NP_001427478.1
	PRSS12	NM_001440550.1		c.1632-906G>A		intron	N/A	NP_001427479.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS12	ENST00000296498.3	TSL:1 MANE Select	c.1631+3651G>A		intron	N/A	ENSP00000296498.3	P56730
	PRSS12	ENST00000864359.1		c.1313+3651G>A		intron	N/A	ENSP00000534418.1
	PRSS12	ENST00000515089.1	TSL:2	n.278-906G>A		intron	N/A

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

African (AFR) AF: 0.0729 AC: 3022 AN: 41478

American (AMR) AF: 0.372 AC: 5663 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3464

East Asian (EAS) AF: 0.132 AC: 682 AN: 5168

South Asian (SAS) AF: 0.344 AC: 1655 AN: 4810

European-Finnish (FIN) AF: 0.283 AC: 2985 AN: 10550

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27175 AN: 67706

Other (OTH) AF: 0.311 AC: 654 AN: 2106

Alfa AF: 0.354 Hom.: 6284

Bravo AF: 0.282

Asia WGS AF: 0.233 AC: 813 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.3
DANN	Benign	0.74
PhyloP100		-0.064
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: rs705837; hg19: chr4-119225940;