Variant 15-51341998-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181789.4(GLDN):c.314G>A(p.Arg105His) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,445,478 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GLDN
NM_181789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.73

Variant links:

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]

GLDN links:

GLDN (HGNC:):

GLDN links:

Genome browser will be placed here

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	Protein	UniProt
GLDN	NM_181789.4 linkuse as main transcript	c.314G>A	p.Arg105His	missense_variant	1/10	ENST00000335449.11	NP_861454.2	Q6ZMI3-1
GLDN	XM_017022121.2 linkuse as main transcript	c.314G>A	p.Arg105His	missense_variant	1/9		XP_016877610.1
GLDN	XM_017022125.1 linkuse as main transcript	c.314G>A	p.Arg105His	missense_variant	1/10		XP_016877614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLDN	ENST00000335449.11 linkuse as main transcript	c.314G>A	p.Arg105His	missense_variant	1/10	2	NM_181789.4	ENSP00000335196.6	Q6ZMI3-1
GLDN	ENST00000558286.5 linkuse as main transcript	n.125G>A		non_coding_transcript_exon_variant	1/3	1
GLDN	ENST00000560690.5 linkuse as main transcript	n.53G>A		non_coding_transcript_exon_variant	1/4	1
GLDN	ENST00000560215.5 linkuse as main transcript	c.200G>A	p.Arg67His	missense_variant	1/4	4		ENSP00000484633.1	A0A087X220

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000882

AC:

AN:

226732

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

124918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000584

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1445478

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.314G>A (p.R105H) alteration is located in exon 1 (coding exon 1) of the GLDN gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Lethal congenital contracture syndrome 11

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

May 04, 2019

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.0093

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Benign

0.050

Eigen_PC

Benign

0.0030

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

0.32

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.34

Sift

Uncertain

0.0080

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.42

MutPred

0.27

Loss of phosphorylation at S108 (P = 0.0738);

MVP

0.85

MPC

0.48

ClinPred

0.92

GERP RS

3.9

Varity_R

0.18

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over