chr11-131911576-G-T

Variant names:

• chr11-131911576-G-T
• rs767842712
• NM_001352005.2:c.95G>T

Variant summary

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

The NM_001352005.2(NTM):​c.95G>T​(p.Arg32Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.40
• 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]

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.95G>T	p.Arg32Leu	missense_variant	Exon 2 of 9	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.95G>T	p.Arg32Leu	missense_variant	Exon 2 of 9		NM_001352005.2	ENSP00000507313.1

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

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.95G>T (p.R32L) alteration is located in exon 1 (coding exon 1) of the NTM gene. This alteration results from a G to T substitution at nucleotide position 95, causing the arginine (R) at amino acid position 32 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	.;.;T;T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	D;.;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.0	L;.;.;L;L;L
PhyloP100		9.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	N;D;N;N;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.026	D;.;T;T;T;T
Sift4G	Benign	0.77	T;.;T;T;T;T
Polyphen		0.0060	B;.;.;P;B;B
Vest4		0.90
MutPred		0.48		Loss of catalytic residue at R32 (P = 0.0219);.;.;Loss of catalytic residue at R32 (P = 0.0219);Loss of catalytic residue at R32 (P = 0.0219);Loss of catalytic residue at R32 (P = 0.0219);
MVP		0.91
MPC		2.6
ClinPred		0.93	D
GERP RS		5.3
PromoterAI		-0.029	Neutral
Varity_R		0.23
gMVP		0.42
Mutation Taster		=44/56	disease causing

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: rs767842712; hg19: chr11-131781470;