Genetic Variant PRSS12:c.*1558_*1559delAA (chr4-118280376-GTT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.239

Publications

1 publications found

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 was made for transcript

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS12	NM_003619.4	MANE Select	c.1558_1559delAA		3_prime_UTR	Exon 13 of 13	NP_003610.2	P56730
	PRSS12	NM_001440549.1		c.1656_1657delAA		3_prime_UTR	Exon 13 of 13	NP_001427478.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRSS12	ENST00000296498.3	TSL:1 MANE Select	c.1558_1559delAA	3_prime_UTR	Exon 13 of 13	ENSP00000296498.3	P56730
SNHG8	ENST00000654083.3		n.1413_1414delTT	non_coding_transcript_exon	Exon 3 of 3
PRSS12	ENST00000864359.1		c.1558_1559delAA	downstream_gene	N/A	ENSP00000534418.1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44494

AN:

151998

Hom.:

8080

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.293

AC:

44495

AN:

152116

Hom.:

8076

Cov.:

AF XY:

0.290

AC XY:

21529

AN XY:

74352

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1540

3081

4621

6162

7702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.148

Hom.:

294

Bravo

AF:

0.287

Asia WGS

AF:

0.236

AC:

824

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual Disability, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over