NM_032342.3:c.976G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032342.3(PGAP4):​c.976G>A​(p.Val326Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PGAP4
NM_032342.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51
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]
TMEM246-AS1 (HGNC:51191): (TMEM246 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2700927).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PGAP4NM_032342.3 linkc.976G>A p.Val326Met 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
PGAP4ENST00000374848.8 linkc.976G>A p.Val326Met missense_variant Exon 2 of 2 1 NM_032342.3 ENSP00000363981.3 Q9BRR3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.976G>A (p.V326M) 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 976, causing the valine (V) at amino acid position 326 to be replaced by a methionine (M). 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
0.33
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.018
T;T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
.;.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.5
L;L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.64
N;N;N
REVEL
Uncertain
0.29
Sift
Uncertain
0.0090
D;D;D
Sift4G
Uncertain
0.015
D;D;D
Polyphen
0.99
D;D;D
Vest4
0.32
MutPred
0.30
Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP
0.24
MPC
1.1
ClinPred
0.77
D
GERP RS
5.7
Varity_R
0.16
gMVP
0.71

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.

Other links and lift over

hg19: chr9-104238399; API