Variant chr1-227816258-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_StrongBS1BS2

The NM_183062.3(PRSS38):c.311+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,607,952 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 96 hom. )

Consequence

PRSS38
NM_183062.3 splice_region, intron

Scores

Splicing: ADA: 0.00002128

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.273

Variant links:

Genes affected

PRSS38 (HGNC:29625): (serine protease 38) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS38 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=-0.89).

BP6

Variant 1-227816258-C-T is Benign according to our data. Variant chr1-227816258-C-T is described in ClinVar as [Benign]. Clinvar id is 771321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.004 (609/152258) while in subpopulation AMR AF= 0.0242 (371/15304). AF 95% confidence interval is 0.0222. There are 8 homozygotes in gnomad4. There are 325 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PRSS38	NM_183062.3 linkuse as main transcript	c.311+6C>T	splice_region_variant, intron_variant	ENST00000366757.4	NP_898885.1	A1L453
PRSS38	NM_001374657.2 linkuse as main transcript	c.311+6C>T	splice_region_variant, intron_variant		NP_001361586.1
PRSS38	XM_011544175.3 linkuse as main transcript	c.311+6C>T	splice_region_variant, intron_variant		XP_011542477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS38	ENST00000366757.4 linkuse as main transcript	c.311+6C>T		splice_region_variant, intron_variant		1	NM_183062.3	ENSP00000355719.3		A1L453

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

602

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0230

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00968

AC:

2395

AN:

247364

Hom.:

AF XY:

0.00717

AC XY:

960

AN XY:

133842

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0529

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0239

Gnomad SAS exome

AF:

0.000461

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00231

AC:

3360

AN:

1455694

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1402

AN XY:

723088

show subpopulations

Gnomad4 AFR exome

AF:

0.000599

Gnomad4 AMR exome

AF:

0.0503

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0184

Gnomad4 SAS exome

AF:

0.000454

Gnomad4 FIN exome

AF:

0.00203

Gnomad4 NFE exome

AF:

0.0000731

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.00400

AC:

609

AN:

152258

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

325

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0228

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00660

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.22

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