chr11-132330155-G-T

Variant names:

• chr11-132330155-G-T
• rs201653643
• NM_001352005.2:c.937G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352005.2(NTM):​c.937G>T​(p.Val313Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000715 in 1,399,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20588017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTM	NM_001352005.2	c.937G>T	p.Val313Leu	missense_variant, splice_region_variant	Exon 8 of 9	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.937G>T	p.Val313Leu	missense_variant, splice_region_variant	Exon 8 of 9		NM_001352005.2	ENSP00000507313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399362 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690188

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078934

Other (OTH) AF: 0.00 AC: 0 AN: 58018

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;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;T
Polyphen		0.0	B;.
Vest4		0.21
MutPred		0.44		Gain of ubiquitination at K314 (P = 0.1047);.;
MVP		0.61
MPC		0.37
ClinPred		0.55	D
GERP RS		5.5
gMVP		0.57
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs201653643; hg19: chr11-132200049;