11-131911634-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352005.2(NTM):c.153G>C(p.Glu51Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTM NM_001352005.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

Genes affected

NTM (HGNC:17941): (neurotrimin) This gene encodes a member of the IgLON (LAMP, OBCAM, Ntm) family of immunoglobulin (Ig) domain-containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules. The encoded protein may promote neurite outgrowth and adhesion via a homophilic mechanism. This gene is closely linked to a related family member, opioid binding protein/cell adhesion molecule-like (OPCML), on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

LOC107984413 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15903303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTM	NM_001352005.2	c.153G>C	p.Glu51Asp	missense_variant	2/9	ENST00000683400.1
LOC107984413	XR_007062957.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTM	ENST00000683400.1	c.153G>C	p.Glu51Asp	missense_variant	2/9		NM_001352005.2	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.153G>C (p.E51D) alteration is located in exon 1 (coding exon 1) of the NTM gene. This alteration results from a G to C substitution at nucleotide position 153, causing the glutamic acid (E) at amino acid position 51 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	23
Dann	Benign	0.91
Eigen	Benign	-0.18
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.86	D;D;D;D;D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N;.;N;N;N
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.82	N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;.;B;B;B
Vest4		0.23
MutPred		0.41		Gain of catalytic residue at E51 (P = 0.0213);.;Gain of catalytic residue at E51 (P = 0.0213);Gain of catalytic residue at E51 (P = 0.0213);Gain of catalytic residue at E51 (P = 0.0213);
MVP		0.34
MPC		0.35
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.40
gMVP		0.39

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: chr11-131781528;