4-118352700-CAC-GAG

Variant names:

• chr4-118352700-CAC-GAG
• NM_003619.4:c.19_21delGTGinsCTC
• PRSS12 p.Val7Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003619.4(PRSS12):​c.19_21delGTGinsCTC​(p.Val7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V7M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS12 NM_003619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.19_21delGTGinsCTC	p.Val7Leu	missense	N/A	NP_003610.2	P56730
	PRSS12	NM_001440549.1		c.19_21delGTGinsCTC	p.Val7Leu	missense	N/A	NP_001427478.1
	PRSS12	NM_001440550.1		c.19_21delGTGinsCTC	p.Val7Leu	missense	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.19_21delGTGinsCTC	p.Val7Leu	missense	N/A	ENSP00000296498.3	P56730
	PRSS12	ENST00000864359.1		c.19_21delGTGinsCTC	p.Val7Leu	missense	N/A	ENSP00000534418.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15

Splicing

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

hg19: chr4-119273855;