15-51342107-G-T

Position:

• chr15-51342107-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181789.4(GLDN):​c.363+60G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,578,554 control chromosomes in the GnomAD database, including 15,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2005 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13359 hom.)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.910

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-51342107-G-T is Benign according to our data. Variant chr15-51342107-G-T is described in ClinVar as [Benign]. Clinvar id is 1222818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.363+60G>T		intron_variant		ENST00000335449.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.363+60G>T		intron_variant		2	NM_181789.4	P1
GLDN	ENST00000558286.5	n.174+60G>T		intron_variant, non_coding_transcript_variant		1
GLDN	ENST00000560690.5	n.140+22G>T		intron_variant, non_coding_transcript_variant		1
GLDN	ENST00000560215.5	c.250+60G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23546 AN: 152082 Hom.: 1996 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.129 AC: 184519 AN: 1426354 Hom.: 13359 Cov.: 32 AF XY: 0.132 AC XY: 93902 AN XY: 710166

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.0679

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.155 AC: 23603 AN: 152200 Hom.: 2005 Cov.: 33 AF XY: 0.156 AC XY: 11643 AN XY: 74424

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.168

Alfa AF: 0.127 Hom.: 170

Bravo AF: 0.164

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs11632569; hg19: chr15-51634304; COSMIC: COSV59092755; COSMIC: COSV59092755;