Variant chr15-51341864-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_181789.4(GLDN):c.180C>T(p.Arg60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00889 in 1,548,716 control chromosomes in the GnomAD database, including 1,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 560 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 481 hom. )

Consequence

GLDN
NM_181789.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.567

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 15-51341864-C-T is Benign according to our data. Variant chr15-51341864-C-T is described in ClinVar as [Benign]. Clinvar id is 1272774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.567 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GLDN	NM_181789.4 linkuse as main transcript	c.180C>T	p.Arg60=	synonymous_variant	1/10	ENST00000335449.11
GLDN	XM_017022121.2 linkuse as main transcript	c.180C>T	p.Arg60=	synonymous_variant	1/9
GLDN	XM_017022125.1 linkuse as main transcript	c.180C>T	p.Arg60=	synonymous_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11 linkuse as main transcript	c.180C>T	p.Arg60=	synonymous_variant	1/10	2	NM_181789.4	P1	Q6ZMI3-1
GLDN	ENST00000560215.5 linkuse as main transcript	c.69C>T	p.Arg23=	synonymous_variant	1/4	4
GLDN	ENST00000558286.5 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7136

AN:

152128

Hom.:

559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.00963

AC:

1446

AN:

150148

Hom.:

117

AF XY:

0.00765

AC XY:

640

AN XY:

83624

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.00760

Gnomad ASJ exome

AF:

0.000976

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000437

Gnomad OTH exome

AF:

0.00535

GnomAD4 exome

AF:

0.00475

AC:

6629

AN:

1396476

Hom.:

481

Cov.:

AF XY:

0.00411

AC XY:

2841

AN XY:

691158

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.00900

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000380

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000301

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.0469

AC:

7144

AN:

152240

Hom.:

560

Cov.:

AF XY:

0.0455

AC XY:

3387

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0251

Hom.:

Bravo

AF:

0.0527

Asia WGS

AF:

0.00637

AC:

AN:

3466

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 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.93

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