Variant 2-44332628-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The ENST00000409411.6(PREPL):c.917T>C(p.Met306Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,880 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

PREPL
ENST00000409411.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

PREPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024042487).

BP6

Variant 2-44332628-A-G is Benign according to our data. Variant chr2-44332628-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 478306.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000617 (94/152340) while in subpopulation AFR AF= 0.00219 (91/41582). AF 95% confidence interval is 0.00182. There are 0 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREPL	NM_001171613.2 linkuse as main transcript	c.917T>C	p.Met306Thr	missense_variant	8/14	ENST00000409411.6	NP_001165084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6 linkuse as main transcript	c.917T>C	p.Met306Thr	missense_variant	8/14	1	NM_001171613.2	ENSP00000387095	P4	Q4J6C6-4

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251090

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000718

AC:

105

AN:

1461540

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000617

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000548

Hom.:

Bravo

AF:

0.000756

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myasthenic syndrome, congenital, 22

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.015

.;.;.;T;T;T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.67

T;.;.;.;.;.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.024

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;.;.;N;N;N;N;.

MutationTaster

Benign

1.0

D;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.28

N;N;N;N;N;N;N;N

REVEL

Benign

0.082

Sift

Benign

0.14

T;T;T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T;T;T

Polyphen

0.0, 0.027

.;.;.;B;B;B;B;B

Vest4

0.53

MVP

0.41

MPC

0.0047

ClinPred

0.063

GERP RS

5.8

Varity_R

0.051

gMVP

0.55

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

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