chr15-51341968-G-A

Position:

• chr15-51341968-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181789.4(GLDN):​c.284G>A​(p.Ser95Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLDN NM_181789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34069836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.284G>A	p.Ser95Asn	missense_variant	1/10	ENST00000335449.11
GLDN	XM_017022121.2	c.284G>A	p.Ser95Asn	missense_variant	1/9
GLDN	XM_017022125.1	c.284G>A	p.Ser95Asn	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.284G>A	p.Ser95Asn	missense_variant	1/10	2	NM_181789.4	P1
GLDN	ENST00000558286.5	n.95G>A		non_coding_transcript_exon_variant	1/3	1
GLDN	ENST00000560690.5	n.23G>A		non_coding_transcript_exon_variant	1/4	1
GLDN	ENST00000560215.5	c.173G>A	p.Ser58Asn	missense_variant	1/4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Jan 10, 2023

The c.284G>A (p.S95N) alteration is located in exon 1 (coding exon 1) of the GLDN gene. This alteration results from a G to A substitution at nucleotide position 284, causing the serine (S) at amino acid position 95 to be replaced by an asparagine (N). 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	Uncertain	0.49
BayesDel_addAF	Benign	0.00060	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.086
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.021	D
Sift4G	Benign	0.25	T
Polyphen		0.65	P
Vest4		0.37
MutPred		0.35		Loss of phosphorylation at S95 (P = 0.0123);
MVP		0.87
MPC		0.22
ClinPred		0.66	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.51

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: chr15-51634165;