9-131510284-G-C

Variant summary

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

The NM_001077365.2(POMT1):​c.724G>C​(p.Ala242Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

POMT1
NM_001077365.2 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.24
Variant links:
Genes affected
POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 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, 0.924

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POMT1NM_001077365.2 linkc.724G>C p.Ala242Pro missense_variant Exon 9 of 20 ENST00000402686.8 NP_001070833.1 Q9Y6A1-2A0A140VKE0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POMT1ENST00000402686.8 linkc.724G>C p.Ala242Pro missense_variant Exon 9 of 20 1 NM_001077365.2 ENSP00000385797.4 Q9Y6A1-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461886
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.59
.;.;D;.;D;.;D;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
T;T;D;T;D;.;T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.97
D
MutationAssessor
Pathogenic
3.8
.;.;.;.;H;.;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.2
D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.77
Sift
Benign
0.065
T;T;D;T;D;T;D;D
Sift4G
Uncertain
0.041
D;D;D;D;D;D;D;D
Polyphen
0.99, 1.0
.;D;.;.;D;D;.;.
Vest4
0.86
MutPred
0.75
.;.;.;.;Gain of relative solvent accessibility (P = 0.0479);.;.;.;
MVP
0.97
MPC
1.0
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.87
gMVP
0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-134385671; API