4-118280432-C-T

Position:

• chr4-118280432-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003619.4(PRSS12):​c.*1504G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,246 control chromosomes in the GnomAD database, including 1,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1328 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PRSS12 NM_003619.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.05

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]

SNHG8 (HGNC:33098): (small nucleolar RNA host gene 8)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-118280432-C-T is Benign according to our data. Variant chr4-118280432-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 347374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS12	NM_003619.4	c.*1504G>A		3_prime_UTR_variant	13/13	ENST00000296498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS12	ENST00000296498.3	c.*1504G>A		3_prime_UTR_variant	13/13	1	NM_003619.4	P1
SNHG8	ENST00000654083.2	n.1282C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17251 AN: 152126 Hom.: 1331 Cov.: 33

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.106

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.113 AC: 17251 AN: 152246 Hom.: 1328 Cov.: 33 AF XY: 0.118 AC XY: 8793 AN XY: 74418

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0917

Gnomad4 EAS AF: 0.0562

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.107

Alfa AF: 0.129 Hom.: 225

Bravo AF: 0.0965

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual disability, autosomal recessive 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.63

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: rs1045817; hg19: chr4-119201587;