rs386834037

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5

The NM_017739.4(POMGNT1):​c.806G>A​(p.Cys269Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

POMGNT1
NM_017739.4 missense

Scores

14
4
1

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.47
Variant links:
Genes affected
POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1
In a region_of_interest Carbohydrate-binding stem domain (size 196) in uniprot entity PMGT1_HUMAN there are 33 pathogenic changes around while only 3 benign (92%) in NM_017739.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.934
PP5
Variant 1-46194347-C-T is Pathogenic according to our data. Variant chr1-46194347-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56607.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-46194347-C-T is described in Lovd as [Likely_pathogenic]. Variant chr1-46194347-C-T is described in Lovd as [Pathogenic]. Variant chr1-46194347-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POMGNT1NM_017739.4 linkuse as main transcriptc.806G>A p.Cys269Tyr missense_variant 9/22 ENST00000371984.8 NP_060209.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POMGNT1ENST00000371984.8 linkuse as main transcriptc.806G>A p.Cys269Tyr missense_variant 9/221 NM_017739.4 ENSP00000361052 P1Q8WZA1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Muscle eye brain disease Pathogenic:1
Likely pathogenic, no assertion criteria providedliterature onlyJuha Muilu Group; Institute for Molecular Medicine Finland (FIMM)-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.87
D;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Uncertain
2.4
M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-8.6
D;D
REVEL
Pathogenic
0.83
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.96
MutPred
0.76
Loss of methylation at K271 (P = 0.0878);Loss of methylation at K271 (P = 0.0878);
MVP
0.99
MPC
1.2
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.95
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs386834037; hg19: chr1-46660019; API