4-118281129-C-T

Variant names:

• chr4-118281129-C-T
• rs17516164
• NM_003619.4:c.*807G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42
• Publications: 3 publications found

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 -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 rank	MANE	Protein	UniProt
PRSS12	NM_003619.4	c.*807G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000296498.3	NP_003610.2
PRSS12	NM_001440549.1	c.*905G>A		3_prime_UTR_variant	Exon 13 of 13		NP_001427478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3	c.*807G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_003619.4	ENSP00000296498.3
SNHG8	ENST00000654083.3	n.2164C>T		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9295 AN: 152010 Hom.: 383 Cov.: 33

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: 11 AN: 44 Hom.: 2 Cov.: 0 AF XY: 0.208 AC XY: 5 AN XY: 24

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.346 AC: 9 AN: 26

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 1 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0611 AC: 9292 AN: 152128 Hom.: 383 Cov.: 33 AF XY: 0.0590 AC XY: 4388 AN XY: 74364

African (AFR) AF: 0.0159 AC: 660 AN: 41502

American (AMR) AF: 0.0338 AC: 517 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0445 AC: 214 AN: 4806

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10572

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0925 AC: 6287 AN: 67998

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0854 Hom.: 311

Bravo AF: 0.0539

Asia WGS AF: 0.0180 AC: 62 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

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.83
DANN	Benign	0.80
PhyloP100		-1.4
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

Other links and lift over

dbSNP: rs17516164; hg19: chr4-119202284;