NM_001352005.2:c.886G>T

Variant names:

• chr11-132314655-G-T
• rs756339914
• NM_001352005.2:c.886G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001352005.2(NTM):​c.886G>T​(p.Val296Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V296M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTM NM_001352005.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTM	NM_001352005.2	c.886G>T	p.Val296Leu	missense_variant	Exon 7 of 9	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.886G>T	p.Val296Leu	missense_variant	Exon 7 of 9		NM_001352005.2	ENSP00000507313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	.;T;.;.;.;T
Eigen	Benign	-0.0016
Eigen_PC	Benign	0.088
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.6	L;L;L;L;.;.
PhyloP100		6.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.5	N;N;N;N;.;.
REVEL	Uncertain	0.37
Sift	Benign	0.10	T;T;T;T;.;.
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.27	B;B;B;B;.;.
Vest4		0.72
MutPred		0.56		Gain of ubiquitination at K300 (P = 0.1306);Gain of ubiquitination at K300 (P = 0.1306);Gain of ubiquitination at K300 (P = 0.1306);Gain of ubiquitination at K300 (P = 0.1306);.;.;
MVP		0.90
MPC		0.81
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.73
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs756339914; hg19: chr11-132184549;