rs201653643

Positions:

• chr11-132330155-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001352005.2(NTM):​c.937G>A​(p.Val313Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00224 in 1,551,686 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: NTM NM_001352005.2 missense, splice_region
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.97

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

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009192795).
• BP6: Variant 11-132330155-G-A is Benign according to our data. Variant chr11-132330155-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 561325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTM	NM_001352005.2	c.937G>A	p.Val313Met	missense_variant, splice_region_variant	8/9	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.937G>A	p.Val313Met	missense_variant, splice_region_variant	8/9		NM_001352005.2	ENSP00000507313	A1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 261 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00182 AC: 286 AN: 156922 Hom.: 1 AF XY: 0.00183 AC XY: 152 AN XY: 83080

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000976

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000528

Gnomad FIN exome AF: 0.00190

Gnomad NFE exome AF: 0.00338

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00230 AC: 3219 AN: 1399350 Hom.: 12 Cov.: 30 AF XY: 0.00222 AC XY: 1535 AN XY: 690184

Gnomad4 AFR exome AF: 0.000380

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.0000794

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000480

Gnomad4 FIN exome AF: 0.00237

Gnomad4 NFE exome AF: 0.00266

Gnomad4 OTH exome AF: 0.00207

GnomAD4 genome AF: 0.00171 AC: 261 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74494

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.00294

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00206 Hom.: 0

Bravo AF: 0.00171

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00377 AC: 12

ExAC AF: 0.00163 AC: 41

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Connective tissue disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Jun 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	.;T
Eigen	Benign	-0.0052
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.0092	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.21	N;.
REVEL	Benign	0.10
Sift	Benign	0.086	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.14	B;.
Vest4		0.31
MVP		0.67
MPC		0.40
ClinPred		0.018	T
GERP RS		5.5
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201653643; hg19: chr11-132200049;