rs139579932

chr11-132335082-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001352005.2(NTM):c.1004C>T(p.Ser335Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,612,568 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: NTM NM_001352005.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.852

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012857556).
• BP6: Variant 11-132335082-C-T is Benign according to our data. Variant chr11-132335082-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 561326.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTM	NM_001352005.2	c.1004C>T	p.Ser335Leu	missense_variant	9/9	ENST00000683400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTM	ENST00000683400.1	c.1004C>T	p.Ser335Leu	missense_variant	9/9		NM_001352005.2	A1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00107 AC: 267 AN: 250132 Hom.: 0 AF XY: 0.00109 AC XY: 148 AN XY: 135320

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.000531

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00113 AC: 1654 AN: 1460470 Hom.: 3 Cov.: 31 AF XY: 0.00109 AC XY: 791 AN XY: 726618

Gnomad4 AFR exome AF: 0.00128

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.000883

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.000834 AC XY: 62 AN XY: 74340

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00128 Hom.: 2

Bravo AF: 0.00113

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00117 AC: 142

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.92
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.013	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N;N;N;.;.
REVEL	Benign	0.14
Sift	Benign	0.093	T;T;T;.;.
Sift4G	Benign	0.67	T;T;T;T;T
Polyphen		0.59	P;P;B;.;.
Vest4		0.16
MVP		0.60
MPC		0.42
ClinPred		0.0045	T
GERP RS		2.2
Varity_R		0.063
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs139579932; hg19: chr11-132204976; COSMIC: COSV66211116; COSMIC: COSV66211116;