chr15-51341811-G-T

Position:

• chr15-51341811-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181789.4(GLDN):​c.127G>T​(p.Gly43Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,361,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: GLDN NM_181789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.127G>T	p.Gly43Trp	missense_variant	1/10	ENST00000335449.11
GLDN	XM_017022121.2	c.127G>T	p.Gly43Trp	missense_variant	1/9
GLDN	XM_017022125.1	c.127G>T	p.Gly43Trp	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.127G>T	p.Gly43Trp	missense_variant	1/10	2	NM_181789.4	P1
GLDN	ENST00000560215.5	c.16G>T	p.Gly6Trp	missense_variant	1/4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1361578 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 671912

Gnomad4 AFR exome AF: 0.0000355

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.127G>T (p.G43W) alteration is located in exon 1 (coding exon 1) of the GLDN gene. This alteration results from a G to T substitution at nucleotide position 127, causing the glycine (G) at amino acid position 43 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.55
MutPred		0.64		Loss of disorder (P = 0.0347);
MVP		0.84
MPC		2.9
ClinPred		0.88	D
GERP RS		1.0
Varity_R		0.17
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-51634008;