15-51360996-G-T

Variant names:

• chr15-51360996-G-T
• rs12148492
• NM_181789.4:c.364-16453G>T

Variant summary

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

The NM_181789.4(GLDN):​c.364-16453G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,212 control chromosomes in the GnomAD database, including 2,220 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 0.15 (2220 hom., cov: 33)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.235 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDN	NM_181789.4	MANE Select	c.364-16453G>T		intron	N/A	NP_861454.2	Q6ZMI3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDN	ENST00000335449.11	TSL:2 MANE Select	c.364-16453G>T		intron	N/A	ENSP00000335196.6	Q6ZMI3-1
	GLDN	ENST00000558286.5	TSL:1	n.174+18949G>T		intron	N/A
	GLDN	ENST00000560690.5	TSL:1	n.141-16453G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23450 AN: 152094 Hom.: 2221 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.154 AC: 23458 AN: 152212 Hom.: 2220 Cov.: 33 AF XY: 0.151 AC XY: 11240 AN XY: 74418

African (AFR) AF: 0.0692 AC: 2876 AN: 41542

American (AMR) AF: 0.242 AC: 3693 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5180

South Asian (SAS) AF: 0.111 AC: 534 AN: 4828

European-Finnish (FIN) AF: 0.126 AC: 1331 AN: 10590

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13776 AN: 67998

Other (OTH) AF: 0.160 AC: 338 AN: 2108

Alfa AF: 0.179 Hom.: 1354

Bravo AF: 0.162

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.37
PhyloP100		-0.39
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: rs12148492; hg19: chr15-51653193;