4-118280376-GTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003619.4(PRSS12):c.*1558_*1559del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,116 control chromosomes in the GnomAD database, including 8,076 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (8076 hom., cov: 21)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS12 NM_003619.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

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 -10 ACMG points.

• BP6: Variant 4-118280376-GTT-G is Benign according to our data. Variant chr4-118280376-GTT-G is described in ClinVar as [Benign]. Clinvar id is 347373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS12	NM_003619.4	c.*1558_*1559del		3_prime_UTR_variant	13/13	ENST00000296498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS12	ENST00000296498.3	c.*1558_*1559del		3_prime_UTR_variant	13/13	1	NM_003619.4	P1
SNHG8	ENST00000654083.2	n.1228_1229del		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44494 AN: 151998 Hom.: 8080 Cov.: 21

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.315

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.293 AC: 44495 AN: 152116 Hom.: 8076 Cov.: 21 AF XY: 0.290 AC XY: 21529 AN XY: 74352

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.314

Alfa AF: 0.148 Hom.: 294

Bravo AF: 0.287

Asia WGS AF: 0.236 AC: 824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3083027; hg19: chr4-119201531;