22-41584562-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002676.3(PMM1):​c.247G>A​(p.Val83Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PMM1
NM_002676.3 missense

Scores

9
5
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00
Variant links:
Genes affected
PMM1 (HGNC:9114): (phosphomannomutase 1) Phosphomannomutase catalyzes the conversion between D-mannose 6-phosphate and D-mannose 1-phosphate which is a substrate for GDP-mannose synthesis. GDP-mannose is used for synthesis of dolichol-phosphate-mannose, which is essential for N-linked glycosylation and thus the secretion of several glycoproteins as well as for the synthesis of glycosyl-phosphatidyl-inositol (GPI) anchored proteins. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PMM1NM_002676.3 linkc.247G>A p.Val83Met missense_variant Exon 3 of 8 ENST00000216259.8 NP_002667.2 Q92871A0A024R1U5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PMM1ENST00000216259.8 linkc.247G>A p.Val83Met missense_variant Exon 3 of 8 1 NM_002676.3 ENSP00000216259.7 Q92871

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251204
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135752
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461658
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727116
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000508
Hom.:
0

ClinVar

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

Submissions by phenotype

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

The c.247G>A (p.V83M) alteration is located in exon 3 (coding exon 3) of the PMM1 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the valine (V) at amino acid position 83 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
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.26
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.94
D
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.84
D
MetaSVM
Pathogenic
1.1
D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.6
D
REVEL
Pathogenic
0.70
Sift
Benign
0.035
D
Sift4G
Benign
0.064
T
Polyphen
0.24
B
Vest4
0.86
MutPred
0.45
Loss of sheet (P = 0.0817);
MVP
0.98
MPC
1.0
ClinPred
0.92
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.64
gMVP
0.77

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.

Other links and lift over

dbSNP: rs1196232803; hg19: chr22-41980566; COSMIC: COSV99348307; COSMIC: COSV99348307; API