15-51341998-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_181789.4(GLDN):c.314G>C(p.Arg105Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000282 in 1,597,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105H) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
GLDN
NM_181789.4 missense
NM_181789.4 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
GLDN (HGNC:29514): (gliomedin) This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDN | NM_181789.4 | c.314G>C | p.Arg105Pro | missense_variant | 1/10 | ENST00000335449.11 | |
GLDN | XM_017022121.2 | c.314G>C | p.Arg105Pro | missense_variant | 1/9 | ||
GLDN | XM_017022125.1 | c.314G>C | p.Arg105Pro | missense_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDN | ENST00000335449.11 | c.314G>C | p.Arg105Pro | missense_variant | 1/10 | 2 | NM_181789.4 | P1 | |
GLDN | ENST00000558286.5 | n.125G>C | non_coding_transcript_exon_variant | 1/3 | 1 | ||||
GLDN | ENST00000560690.5 | n.53G>C | non_coding_transcript_exon_variant | 1/4 | 1 | ||||
GLDN | ENST00000560215.5 | c.203G>C | p.Arg68Pro | missense_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000838 AC: 19AN: 226732Hom.: 0 AF XY: 0.000104 AC XY: 13AN XY: 124918
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GnomAD4 exome AF: 0.0000304 AC: 44AN: 1445478Hom.: 0 Cov.: 31 AF XY: 0.0000431 AC XY: 31AN XY: 719498
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152362Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74502
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2022 | The c.314G>C (p.R105P) alteration is located in exon 1 (coding exon 1) of the GLDN gene. This alteration results from a G to C substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.0079);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at