chr4-118308551-C-G

Variant names:

• chr4-118308551-C-G
• NM_003619.4:c.1516G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003619.4(PRSS12):​c.1516G>C​(p.Glu506Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,724 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRSS12 NM_003619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3681609).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS12	NM_003619.4	c.1516G>C	p.Glu506Gln	missense_variant	Exon 8 of 13	ENST00000296498.3	NP_003610.2
PRSS12	XM_011532387.3	c.1516G>C	p.Glu506Gln	missense_variant	Exon 8 of 9		XP_011530689.1
PRSS12	XM_005263318.5	c.1516G>C	p.Glu506Gln	missense_variant	Exon 8 of 10		XP_005263375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3	c.1516G>C	p.Glu506Gln	missense_variant	Exon 8 of 13	1	NM_003619.4	ENSP00000296498.3
PRSS12	ENST00000515089.1	n.103G>C		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461724 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.13	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.17
Sift	Benign	0.18	T
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.30		Gain of methylation at K508 (P = 0.0954);
MVP		0.69
MPC		0.77
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-119229706;