11-132330155-G-C

Variant names:

• chr11-132330155-G-C
• NM_001352005.2:c.937G>C
• NTM p.Val313Leu

Variant summary

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

The NM_001352005.2(NTM):​c.937G>C​(p.Val313Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. V313M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTM NM_001352005.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352005.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTM	NM_001352005.2	MANE Select	c.937G>C	p.Val313Leu	missense splice_region	Exon 8 of 9	NP_001338934.1	B7Z1Z5
	NTM	NM_001352001.2		c.973G>C	p.Val325Leu	missense splice_region	Exon 9 of 10	NP_001338930.1
	NTM	NM_001352002.2		c.973G>C	p.Val325Leu	missense splice_region	Exon 8 of 9	NP_001338931.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTM	ENST00000683400.1	MANE Select	c.937G>C	p.Val313Leu	missense splice_region	Exon 8 of 9	ENSP00000507313.1	B7Z1Z5
	NTM	ENST00000425719.6	TSL:1	c.937G>C	p.Val313Leu	missense splice_region	Exon 7 of 8	ENSP00000396722.2	Q9P121-4
	NTM	ENST00000374786.5	TSL:1	c.935-4891G>C		intron	N/A	ENSP00000363918.1	Q9P121-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.094
Sift	Benign	0.30	T
Sift4G	Benign	0.35	T
gMVP		0.57
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: -2
DS_DG_spliceai		0.24		Position offset: 30

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-132200049;