Variant 9-101476959-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032342.3(PGAP4):c.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,614,040 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 4 hom. )

Consequence

PGAP4
NM_032342.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

Variant links:

Genes affected

PGAP4 (HGNC:28180): (post-GPI attachment to proteins GalNAc transferase 4) Enables glycosyltransferase activity. Involved in GPI anchor biosynthetic process. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

PGAP4 links:

TMEM246-AS1 (HGNC:51191): (TMEM246 antisense RNA 1)

TMEM246-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051990956).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP4	NM_032342.3 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	2/2	ENST00000374848.8
TMEM246-AS1	NR_121573.1 linkuse as main transcript	n.337+1917C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP4	ENST00000374848.8 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	2/2	1	NM_032342.3	P1
TMEM246-AS1	ENST00000424154.6 linkuse as main transcript	n.212-2881C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251308

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000216

AC:

316

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

167

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000164

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

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

Feb 01, 2023

The c.134G>A (p.R45Q) alteration is located in exon 2 (coding exon 1) of the TMEM246 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 to be replaced by a glutamine (Q). 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

0.089

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

.;.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.066

Sift

Benign

0.093

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.96

D;D;D

Vest4

0.17

MVP

0.15

MPC

0.46

ClinPred

0.052

GERP RS

4.5

Varity_R

0.13

gMVP

0.63

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