Variant 16-372208-C-T 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_021259.3(PGAP6):c.2095G>A(p.Val699Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,611,006 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 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

PGAP6
NM_021259.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.430

Variant links:

Genes affected

PGAP6 (HGNC:17205): (post-GPI attachment to proteins 6) Predicted to enable phospholipase A2 activity. Located in extracellular exosome and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

PGAP6 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=0.011677891).

BP6

Variant 16-372208-C-T is Benign according to our data. Variant chr16-372208-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3211704.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3 linkuse as main transcript	c.2095G>A	p.Val699Ile	missense_variant	13/13	ENST00000431232.7	NP_067082.2	Q9HCN3
PGAP6	XM_047434413.1 linkuse as main transcript	c.1516G>A	p.Val506Ile	missense_variant	14/14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PGAP6	ENST00000431232.7 linkuse as main transcript	c.2095G>A	p.Val699Ile	missense_variant	13/13	1	NM_021259.3	ENSP00000401338.2	Q9HCN3
PGAP6	ENST00000250930.7 linkuse as main transcript	c.1516G>A	p.Val506Ile	missense_variant	13/13	2		ENSP00000250930.3	K4DI83
PGAP6	ENST00000424078.5 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	4/4	3		ENSP00000397620.1	H0Y5B2

Frequencies

GnomAD3 genomes

AF:

0.0000398

AC:

AN:

150634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

249518

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1460372

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000115

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000398

AC:

AN:

150634

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.0000445

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Jan 26, 2022

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

0.060

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0021

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.032

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.027

B;.

Vest4

0.028

MutPred

0.27

Loss of catalytic residue at V699 (P = 0.018);.;

MVP

0.055

MPC

0.038

ClinPred

0.023

GERP RS

-0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.011

gMVP

0.13

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