Variant 16-372202-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021259.3(PGAP6):c.2101A>G(p.Met701Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,612,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

PGAP6
NM_021259.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.534

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07511327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3 linkuse as main transcript	c.2101A>G	p.Met701Val	missense_variant	13/13	ENST00000431232.7	NP_067082.2	Q9HCN3
PGAP6	XM_047434413.1 linkuse as main transcript	c.1522A>G	p.Met508Val	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.2101A>G	p.Met701Val	missense_variant	13/13	1	NM_021259.3	ENSP00000401338.2	Q9HCN3
PGAP6	ENST00000250930.7 linkuse as main transcript	c.1522A>G	p.Met508Val	missense_variant	13/13	2		ENSP00000250930.3	K4DI83
PGAP6	ENST00000424078.5 linkuse as main transcript	c.502A>G	p.Met168Val	missense_variant	4/4	3		ENSP00000397620.1	H0Y5B2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000881

AC:

AN:

249716

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000849

AC:

124

AN:

1460432

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

726504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000710

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000743

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.2101A>G (p.M701V) alteration is located in exon 13 (coding exon 13) of the TMEM8A gene. This alteration results from a A to G substitution at nucleotide position 2101, causing the methionine (M) at amino acid position 701 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0066

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.078

Sift

Benign

0.040

D;D

Sift4G

Benign

0.091

T;T

Polyphen

0.56

P;.

Vest4

0.36

MutPred

0.41

Gain of glycosylation at S700 (P = 0.0403);.;

MVP

0.14

MPC

0.14

ClinPred

0.058

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.45

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