11-132146404-A-C

Variant names:

• chr11-132146404-A-C
• NM_001352005.2:c.290A>C

Variant summary

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

The NM_001352005.2(NTM):​c.290A>C​(p.Gln97Pro) 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: 9.31
• 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.290A>C	p.Gln97Pro	missense	Exon 3 of 9	NP_001338934.1	B7Z1Z5
	NTM	NM_001352001.2		c.290A>C	p.Gln97Pro	missense	Exon 3 of 10	NP_001338930.1
	NTM	NM_001352002.2		c.290A>C	p.Gln97Pro	missense	Exon 2 of 9	NP_001338931.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTM	ENST00000683400.1	MANE Select	c.290A>C	p.Gln97Pro	missense	Exon 3 of 9	ENSP00000507313.1	B7Z1Z5
	NTM	ENST00000425719.6	TSL:1	c.290A>C	p.Gln97Pro	missense	Exon 2 of 8	ENSP00000396722.2	Q9P121-4
	NTM	ENST00000374786.5	TSL:1	c.290A>C	p.Gln97Pro	missense	Exon 2 of 7	ENSP00000363918.1	Q9P121-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
PhyloP100		9.3
PromoterAI		-0.0036	Neutral
Varity_R		0.91
gMVP		0.83
Mutation Taster		=33/67	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

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

Other links and lift over

hg19: chr11-132016298;