chr15-51341988-C-T

Position:

• chr15-51341988-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181789.4(GLDN):​c.304C>T​(p.Pro102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLDN NM_181789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.248

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038998187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDN	NM_181789.4	c.304C>T	p.Pro102Ser	missense_variant	1/10	ENST00000335449.11	NP_861454.2
GLDN	XM_017022121.2	c.304C>T	p.Pro102Ser	missense_variant	1/9		XP_016877610.1
GLDN	XM_017022125.1	c.304C>T	p.Pro102Ser	missense_variant	1/10		XP_016877614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLDN	ENST00000335449.11	c.304C>T	p.Pro102Ser	missense_variant	1/10	2	NM_181789.4	ENSP00000335196.6
GLDN	ENST00000558286.5	n.115C>T		non_coding_transcript_exon_variant	1/3	1
GLDN	ENST00000560690.5	n.43C>T		non_coding_transcript_exon_variant	1/4	1
GLDN	ENST00000560215.5	c.190C>T	p.Pro64Ser	missense_variant	1/4	4		ENSP00000484633.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Sep 02, 2024

The c.304C>T (p.P102S) alteration is located in exon 1 (coding exon 1) of the GLDN gene. This alteration results from a C to T substitution at nucleotide position 304, causing the proline (P) at amino acid position 102 to be replaced by a serine (S). 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	0.067
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.6
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.49	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.11
Sift	Benign	0.94	T
Sift4G	Benign	0.35	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.38		Gain of phosphorylation at P102 (P = 0.0205);
MVP		0.27
MPC		0.11
ClinPred		0.045	T
GERP RS		0.53
Varity_R		0.019
gMVP		0.31

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: chr15-51634185;