Variant chr4-118281129-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003619.4(PRSS12):c.*807G>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 0.0611 in 152,172 control chromosomes in the GnomAD database, including 385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 383 hom., cov: 33)

Exomes 𝑓: 0.25 ( 2 hom. )

Consequence

PRSS12
NM_003619.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.42

Variant links:

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 links:

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

SNHG8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-118281129-C-T is Benign according to our data. Variant chr4-118281129-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 347378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS12	NM_003619.4 linkuse as main transcript	c.*807G>A		3_prime_UTR_variant	13/13	ENST00000296498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS12	ENST00000296498.3 linkuse as main transcript	c.*807G>A		3_prime_UTR_variant	13/13	1	NM_003619.4	P1
SNHG8	ENST00000654083.2 linkuse as main transcript	n.1979C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9295

AN:

152010

Hom.:

383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.0495

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.0546

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.208

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.0714

GnomAD4 genome

AF:

0.0611

AC:

9292

AN:

152128

Hom.:

383

Cov.:

AF XY:

0.0590

AC XY:

4388

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.0994

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0445

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.0925

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0855

Hom.:

285

Bravo

AF:

0.0539

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.83

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over