NM_002066.3:c.173T>C

Variant summary

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

The NM_002066.3(GML):​c.173T>C​(p.Ile58Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I58N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GML
NM_002066.3 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85
Variant links:
Genes affected
GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.12854448).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GMLNM_002066.3 linkc.173T>C p.Ile58Thr missense_variant Exon 3 of 4 ENST00000220940.2 NP_002057.1 Q99445

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GMLENST00000220940.2 linkc.173T>C p.Ile58Thr missense_variant Exon 3 of 4 1 NM_002066.3 ENSP00000220940.1 Q99445
GMLENST00000522728.5 linkc.173T>C p.Ile58Thr missense_variant Exon 3 of 5 3 ENSP00000430799.1 E5RI31

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1288720
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
650086
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Benign
0.92
DEOGEN2
Benign
0.027
.;T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.078
N
LIST_S2
Benign
0.45
T;T
M_CAP
Benign
0.00069
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
.;L
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-4.2
D;N
REVEL
Benign
0.13
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.40
.;B
Vest4
0.42
MutPred
0.47
Loss of stability (P = 0.0853);Loss of stability (P = 0.0853);
MVP
0.15
MPC
0.29
ClinPred
0.54
D
GERP RS
3.4
Varity_R
0.13
gMVP
0.27

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: rs765865698; hg19: chr8-143922633; API