11-131911524-G-A

Variant names:

• chr11-131911524-G-A
• ENST00000425719.6:c.43G>A

Variant summary

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

The NM_001352002.2(NTM):​c.43G>A​(p.Val15Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,874 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: 0.0000021 (0 hom.)
• Consequence: NTM NM_001352002.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.41

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]

ENSG00000294035 (HGNC:):

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.83-40G>A		intron_variant	Intron 1 of 8	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.83-40G>A		intron_variant	Intron 1 of 8		NM_001352005.2	ENSP00000507313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43G>A (p.V15M) alteration is located in exon 1 (coding exon 1) of the NTM gene. This alteration results from a G to A substitution at nucleotide position 43, causing the valine (V) at amino acid position 15 to be replaced by a methionine (M). 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	0.22
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.81	L;L;L
PhyloP100		7.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.043	D;D;D
Sift4G	Benign	0.074	T;T;T
Polyphen		0.90	P;B;B
Vest4		0.48
MutPred		0.47		Loss of catalytic residue at V15 (P = 0.0688);Loss of catalytic residue at V15 (P = 0.0688);Loss of catalytic residue at V15 (P = 0.0688);
MVP		0.86
MPC		2.7
ClinPred		0.80	D
GERP RS		5.3
PromoterAI		0.074	Neutral
Varity_R		0.14
gMVP		0.21
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

hg19: chr11-131781418;