NM_181789.4:c.364-16386T>G

Variant names:

• chr15-51361063-T-G
• rs2445781
• NM_181789.4:c.364-16386T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181789.4(GLDN):​c.364-16386T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,070 control chromosomes in the GnomAD database, including 9,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9105 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181789.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDN	NM_181789.4	MANE Select	c.364-16386T>G		intron	N/A	NP_861454.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDN	ENST00000335449.11	TSL:2 MANE Select	c.364-16386T>G		intron	N/A	ENSP00000335196.6
	GLDN	ENST00000558286.5	TSL:1	n.174+19016T>G		intron	N/A
	GLDN	ENST00000560690.5	TSL:1	n.141-16386T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49922 AN: 151952 Hom.: 9097 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 49976 AN: 152070 Hom.: 9105 Cov.: 32 AF XY: 0.321 AC XY: 23841 AN XY: 74344

African (AFR) AF: 0.476 AC: 19749 AN: 41446

American (AMR) AF: 0.386 AC: 5892 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1077 AN: 3470

East Asian (EAS) AF: 0.143 AC: 738 AN: 5174

South Asian (SAS) AF: 0.233 AC: 1120 AN: 4814

European-Finnish (FIN) AF: 0.166 AC: 1755 AN: 10592

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18651 AN: 67968

Other (OTH) AF: 0.321 AC: 680 AN: 2116

Alfa AF: 0.300 Hom.: 4290

Bravo AF: 0.357

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.61
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2445781; hg19: chr15-51653260;