Variant chr6-36963324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_153370.3(PI16):c.982G>A(p.Val328Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

PI16
NM_153370.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.236

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:

PI16 (HGNC:):

PI16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029053807).

BP6

Variant 6-36963324-G-A is Benign according to our data. Variant chr6-36963324-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2594039.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI16	NM_153370.3 linkuse as main transcript	c.982G>A	p.Val328Met	missense_variant	5/7	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.982G>A	p.Val328Met	missense_variant	5/7	1	NM_153370.3	ENSP00000362778.3	Q6UXB8-1
PI16	ENST00000611814.4 linkuse as main transcript	c.982G>A	p.Val328Met	missense_variant	6/8	5		ENSP00000478888.1	Q6UXB8-1
PI16	ENST00000647861.1 linkuse as main transcript	c.982G>A	p.Val328Met	missense_variant	7/9			ENSP00000497550.1	Q6UXB8-1
PI16	ENST00000491324.1 linkuse as main transcript	n.44+291G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251412

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000917

AC:

134

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000562

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000706

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

DANN

Benign

0.32

DEOGEN2

Benign

0.0097

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.50

.;T;.

M_CAP

Benign

0.0066

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.46

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.11

.;.;N

REVEL

Benign

0.066

Sift

Benign

0.42

.;.;T

Sift4G

Benign

0.67

.;T;T

Polyphen

0.012

B;B;B

Vest4

0.040, 0.038

MVP

0.085

MPC

0.32

ClinPred

0.0093

GERP RS

0.71

Varity_R

0.023

gMVP

0.066

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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