Genetic Variant PGAP4:p.Asn203Asp (chr9-101476486-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032342.3(PGAP4):c.607A>G(p.Asn203Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PGAP4
NM_032342.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

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 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=0.10429633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP4	NM_032342.3 link	c.607A>G	p.Asn203Asp	missense_variant	Exon 2 of 2	ENST00000374848.8	NP_115718.1	Q9BRR3A0A024R188

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP4	ENST00000374848.8 link	c.607A>G	p.Asn203Asp	missense_variant	Exon 2 of 2	1	NM_032342.3	ENSP00000363981.3		Q9BRR3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152126

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

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:

0.00

Gnomad4 OTH

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

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.607A>G (p.N203D) alteration is located in exon 2 (coding exon 1) of the TMEM246 gene. This alteration results from a A to G substitution at nucleotide position 607, causing the asparagine (N) at amino acid position 203 to be replaced by an aspartic acid (D). 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

0.085

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.038

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

.;.;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

L;L;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.094

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0090

B;B;B

Vest4

0.14

MutPred

0.28

Gain of phosphorylation at T201 (P = 0.0872);Gain of phosphorylation at T201 (P = 0.0872);Gain of phosphorylation at T201 (P = 0.0872);

MVP

0.19

MPC

0.45

ClinPred

0.52

GERP RS

3.4

Varity_R

0.12

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over