Variant 15-51377428-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_181789.4(GLDN):c.364-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,607,702 control chromosomes in the GnomAD database, including 30,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.15 ( 1994 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28295 hom. )

Consequence

GLDN
NM_181789.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.67

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 Benign. Variant got -16 ACMG points.

BP6

Variant 15-51377428-A-C is Benign according to our data. Variant chr15-51377428-A-C is described in ClinVar as [Benign]. Clinvar id is 1225115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDN	NM_181789.4 linkuse as main transcript	c.364-21A>C		intron_variant		ENST00000335449.11	NP_861454.2	Q6ZMI3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLDN	ENST00000335449.11 linkuse as main transcript	c.364-21A>C		intron_variant		2	NM_181789.4	ENSP00000335196.6		Q6ZMI3-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22284

AN:

152090

Hom.:

1995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.168

AC:

42143

AN:

250168

Hom.:

3922

AF XY:

0.175

AC XY:

23697

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.0364

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.0754

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.192

AC:

279871

AN:

1455494

Hom.:

28295

Cov.:

AF XY:

0.193

AC XY:

140063

AN XY:

724412

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.0788

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.146

AC:

22278

AN:

152208

Hom.:

1994

Cov.:

AF XY:

0.145

AC XY:

10785

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.0822

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.181

Hom.:

1011

Bravo

AF:

0.140

TwinsUK

AF:

0.204

AC:

756

ALSPAC

AF:

0.210

AC:

811

ESP6500AA

AF:

0.0453

AC:

199

ESP6500EA

AF:

0.210

AC:

1805

ExAC

AF:

0.169

AC:

20488

Asia WGS

AF:

0.141

AC:

490

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

2.5

DANN

Benign

0.79

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0027

PROVEAN

Benign

-0.57

Sift

Benign

0.50

Sift4G

Benign

0.28

GERP RS

4.9

La Branchor

0.87

BranchPoint Hunter

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.36

Position offset: 21

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