rs12592797

Variant names:

• chr15-51347439-C-A
• rs12592797
• NM_181789.4:c.363+5392C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-51347439-C-A
• chr15-51347439-C-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.363+5392C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,074 control chromosomes in the GnomAD database, including 6,652 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 0.24 (6652 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDN	NM_181789.4	c.363+5392C>A		intron_variant	Intron 1 of 9	ENST00000335449.11	NP_861454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDN	ENST00000335449.11	c.363+5392C>A		intron_variant	Intron 1 of 9	2	NM_181789.4	ENSP00000335196.6
GLDN	ENST00000558286.5	n.174+5392C>A		intron_variant	Intron 1 of 2	1
GLDN	ENST00000560690.5	n.140+5354C>A		intron_variant	Intron 1 of 3	1
GLDN	ENST00000560215.5	c.249+5392C>A		intron_variant	Intron 1 of 3	4		ENSP00000484633.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36144 AN: 151956 Hom.: 6626 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.238 AC: 36233 AN: 152074 Hom.: 6652 Cov.: 32 AF XY: 0.236 AC XY: 17554 AN XY: 74360

African (AFR) AF: 0.515 AC: 21326 AN: 41444

American (AMR) AF: 0.182 AC: 2788 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1065 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1246 AN: 4810

European-Finnish (FIN) AF: 0.0635 AC: 673 AN: 10594

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8025 AN: 67986

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.0914 Hom.: 217

Bravo AF: 0.257

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.62
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: rs12592797; hg19: chr15-51639636;