rs373311928

Variant names:

• chr4-118352412-C-A
• rs373311928
• NM_003619.4:c.309G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-118352412-C-A
• chr4-118352412-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003619.4(PRSS12):​c.309G>T​(p.Thr103Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T103T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PRSS12 NM_003619.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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: Illumina, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS12	NM_003619.4	c.309G>T	p.Thr103Thr	synonymous_variant	Exon 1 of 13	ENST00000296498.3	NP_003610.2
PRSS12	NM_001440549.1	c.309G>T	p.Thr103Thr	synonymous_variant	Exon 1 of 13		NP_001427478.1
PRSS12	NM_001440550.1	c.309G>T	p.Thr103Thr	synonymous_variant	Exon 1 of 9		NP_001427479.1
PRSS12	NM_001440551.1	c.309G>T	p.Thr103Thr	synonymous_variant	Exon 1 of 10		NP_001427480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3	c.309G>T	p.Thr103Thr	synonymous_variant	Exon 1 of 13	1	NM_003619.4	ENSP00000296498.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382576 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 681852

African (AFR) AF: 0.00 AC: 0 AN: 31322

American (AMR) AF: 0.00 AC: 0 AN: 35100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24814

East Asian (EAS) AF: 0.00 AC: 0 AN: 35742

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076920

Other (OTH) AF: 0.00 AC: 0 AN: 57616

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.8
DANN	Benign	0.90
PhyloP100		-1.4

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: rs373311928; hg19: chr4-119273567;