chr4-118280376-GTT-G

Variant names:

• chr4-118280376-GTT-G
• rs3083027
• NM_003619.4:c.*1558_*1559delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003619.4(PRSS12):​c.*1558_*1559delAA 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRSS12	NM_003619.4	c.*1558_*1559delAA		3_prime_UTR_variant	Exon 13 of 13	ENST00000296498.3	NP_003610.2
PRSS12	NM_001440549.1	c.*1656_*1657delAA		3_prime_UTR_variant	Exon 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3	c.*1558_*1559delAA		3_prime_UTR_variant	Exon 13 of 13	1	NM_003619.4	ENSP00000296498.3
SNHG8	ENST00000654083.3	n.1413_1414delTT		non_coding_transcript_exon_variant	Exon 3 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0886 AC: 3677 AN: 41522

American (AMR) AF: 0.372 AC: 5684 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3470

East Asian (EAS) AF: 0.131 AC: 680 AN: 5182

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4826

European-Finnish (FIN) AF: 0.283 AC: 2985 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27234 AN: 67946

Other (OTH) AF: 0.314 AC: 662 AN: 2108

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs3083027; hg19: chr4-119201531;