Variant rs1405069 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153370.3(PI16):c.148A>C(p.Thr50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,612,844 control chromosomes in the GnomAD database, including 176,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.53 ( 22417 hom., cov: 31)

Exomes 𝑓: 0.46 ( 154122 hom. )

Consequence

PI16
NM_153370.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

Variant links:

Genes affected

PI16 (HGNC:21245): (peptidase inhibitor 16) Predicted to enable peptidase inhibitor activity. Predicted to be involved in negative regulation of peptidase activity. Predicted to act upstream of or within negative regulation of cell growth involved in cardiac muscle cell development. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PI16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6780249E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI16	NM_153370.3 linkuse as main transcript	c.148A>C	p.Thr50Pro	missense_variant	1/7	ENST00000373674.4	NP_699201.2	Q6UXB8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PI16	ENST00000373674.4 linkuse as main transcript	c.148A>C	p.Thr50Pro	missense_variant	1/7	1	NM_153370.3	ENSP00000362778.3	Q6UXB8-1
PI16	ENST00000611814.4 linkuse as main transcript	c.148A>C	p.Thr50Pro	missense_variant	2/8	5		ENSP00000478888.1	Q6UXB8-1
PI16	ENST00000647861.1 linkuse as main transcript	c.148A>C	p.Thr50Pro	missense_variant	3/9			ENSP00000497550.1	Q6UXB8-1

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80257

AN:

151800

Hom.:

22373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.508

GnomAD3 exomes

AF:

0.478

AC:

118591

AN:

248036

Hom.:

29409

AF XY:

0.465

AC XY:

62551

AN XY:

134394

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.607

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.466

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.447

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.455

AC:

665095

AN:

1460926

Hom.:

154122

Cov.:

AF XY:

0.452

AC XY:

328609

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.601

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.398

Gnomad4 FIN exome

AF:

0.425

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.464

GnomAD4 genome

AF:

0.529

AC:

80360

AN:

151918

Hom.:

22417

Cov.:

AF XY:

0.526

AC XY:

39074

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.703

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.480

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.425

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.462

Hom.:

34751

Bravo

AF:

0.552

TwinsUK

AF:

0.454

AC:

1685

ALSPAC

AF:

0.436

AC:

1682

ESP6500AA

AF:

0.693

AC:

3052

ESP6500EA

AF:

0.446

AC:

3833

ExAC

AF:

0.473

AC:

57480

Asia WGS

AF:

0.410

AC:

1426

AN:

3478

EpiCase

AF:

0.446

EpiControl

AF:

0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.034

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.85

DANN

Benign

0.14

DEOGEN2

Benign

0.00043

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.023

.;T;.

MetaRNN

Benign

0.0000027

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

2.3

.;.;N

REVEL

Benign

0.060

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.064, 0.047

MPC

0.40

ClinPred

0.0020

GERP RS

3.7

Varity_R

0.075

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over