Genetic Variant NM_001352005.2:c.937G>T (chr11-132330155-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 12/20 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.97

Publications

0 publications found

Variant links:

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]

NTM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399362

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.00

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078934

Other (OTH)

AF:

0.00

AC:

AN:

58018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.11

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.67

M_CAP

Benign

0.014

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

PhyloP100

6.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.10

REVEL

Benign

0.094

Sift

Benign

0.30

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.21

MutPred

0.44

Gain of ubiquitination at K314 (P = 0.1047)

MVP

0.61

MPC

0.37

ClinPred

0.55

GERP RS

5.5

gMVP

0.57

Mutation Taster

=73/27

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over