Variant 16-377479-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000431232.7(PGAP6):c.406A>G(p.Thr136Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,607,742 control chromosomes in the GnomAD database, including 266,285 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 0.57 ( 25186 hom., cov: 33)

Exomes 𝑓: 0.57 ( 241099 hom. )

Consequence

PGAP6
ENST00000431232.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.234334E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3 linkuse as main transcript	c.406A>G	p.Thr136Ala	missense_variant	3/13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1 linkuse as main transcript	c.-174A>G		5_prime_UTR_variant	4/14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PGAP6	ENST00000431232.7 linkuse as main transcript	c.406A>G	p.Thr136Ala	missense_variant	3/13	1	NM_021259.3	ENSP00000401338	P2
PGAP6	ENST00000250930.7 linkuse as main transcript	c.-174A>G		5_prime_UTR_variant	3/13	2		ENSP00000250930	A2
PGAP6	ENST00000427313.5 linkuse as main transcript	c.-174A>G		5_prime_UTR_variant	3/5	4		ENSP00000410987
PGAP6	ENST00000476735.1 linkuse as main transcript	n.643A>G		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86635

AN:

151786

Hom.:

25157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.538

AC:

128380

AN:

238422

Hom.:

35953

AF XY:

0.553

AC XY:

71849

AN XY:

129820

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.309

Gnomad SAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.555

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.536

GnomAD4 exome

AF:

0.571

AC:

831857

AN:

1455840

Hom.:

241099

Cov.:

AF XY:

0.575

AC XY:

416365

AN XY:

723736

show subpopulations

Gnomad4 AFR exome

AF:

0.642

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.707

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.579

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.571

AC:

86727

AN:

151902

Hom.:

25186

Cov.:

AF XY:

0.571

AC XY:

42376

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.704

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.569

Gnomad4 OTH

AF:

0.522

Alfa

AF:

0.551

Hom.:

28530

Bravo

AF:

0.557

TwinsUK

AF:

0.593

AC:

2199

ALSPAC

AF:

0.581

AC:

2240

ESP6500AA

AF:

0.623

AC:

2729

ESP6500EA

AF:

0.567

AC:

4876

ExAC

AF:

0.538

AC:

64606

Asia WGS

AF:

0.539

AC:

1873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.018

DANN

Benign

0.21

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.18

MetaRNN

Benign

0.000012

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

0.16

REVEL

Benign

0.019

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0080

MPC

0.041

ClinPred

0.0017

GERP RS

0.98

Varity_R

0.013

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over