Variant 15-51341970-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181789.4(GLDN):c.286C>G(p.His96Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000083 in 1,445,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

GLDN
NM_181789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

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:

Genome browser will be placed here

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=0.20634976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GLDN	NM_181789.4 linkuse as main transcript	c.286C>G	p.His96Asp	missense_variant	1/10	ENST00000335449.11
GLDN	XM_017022121.2 linkuse as main transcript	c.286C>G	p.His96Asp	missense_variant	1/9
GLDN	XM_017022125.1 linkuse as main transcript	c.286C>G	p.His96Asp	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11 linkuse as main transcript	c.286C>G	p.His96Asp	missense_variant	1/10	2	NM_181789.4	P1	Q6ZMI3-1
GLDN	ENST00000558286.5 linkuse as main transcript	n.97C>G		non_coding_transcript_exon_variant	1/3	1
GLDN	ENST00000560690.5 linkuse as main transcript	n.25C>G		non_coding_transcript_exon_variant	1/4	1
GLDN	ENST00000560215.5 linkuse as main transcript	c.175C>G	p.His59Asp	missense_variant	1/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000488

AC:

AN:

225470

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

124652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000322

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:

0.00000830

AC:

AN:

1445302

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000269

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000509

AC:

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

Oct 20, 2021

The c.286C>G (p.H96D) alteration is located in exon 1 (coding exon 1) of the GLDN gene. This alteration results from a C to G substitution at nucleotide position 286, causing the histidine (H) at amino acid position 96 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.040

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.086

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.21

MetaSVM

Uncertain

-0.038

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.92

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.54

REVEL

Uncertain

0.49

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.010

Polyphen

0.48

Vest4

0.54

MutPred

0.33

Gain of relative solvent accessibility (P = 0.0166);

MVP

0.82

MPC

0.18

ClinPred

0.10

GERP RS

4.7

Varity_R

0.22

gMVP

0.40

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