rs139579932

Variant names:

• chr11-132335082-C-T
• rs139579932
• NM_001352005.2:c.1004C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 16/22 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.852
• Publications: 5 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: Benign. The variant received -16 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 VariationId is 561326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTM	NM_001352005.2	MANE Select	c.1004C>T	p.Ser335Leu	missense	Exon 9 of 9	NP_001338934.1
	NTM	NM_001352001.2		c.1040C>T	p.Ser347Leu	missense	Exon 10 of 10	NP_001338930.1
	NTM	NM_001352002.2		c.1040C>T	p.Ser347Leu	missense	Exon 9 of 9	NP_001338931.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTM	ENST00000683400.1	MANE Select	c.1004C>T	p.Ser335Leu	missense	Exon 9 of 9	ENSP00000507313.1
	NTM	ENST00000425719.6	TSL:1	c.1004C>T	p.Ser335Leu	missense	Exon 8 of 8	ENSP00000396722.2
	NTM	ENST00000374786.5	TSL:1	c.971C>T	p.Ser324Leu	missense	Exon 7 of 7	ENSP00000363918.1

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

GnomAD2 exomes AF: 0.00107 AC: 267 AN: 250132 AF XY: 0.00109

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 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

African (AFR) AF: 0.00128 AC: 43 AN: 33474

American (AMR) AF: 0.00161 AC: 72 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 61 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86238

European-Finnish (FIN) AF: 0.000883 AC: 46 AN: 52094

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00121 AC: 1345 AN: 1111964

Other (OTH) AF: 0.00131 AC: 79 AN: 60382

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

African (AFR) AF: 0.00111 AC: 46 AN: 41500

American (AMR) AF: 0.000654 AC: 10 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68006

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00133 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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Connective tissue disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.85
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.093	T
Sift4G	Benign	0.67	T
Polyphen		0.59	P
Vest4		0.16
MVP		0.60
MPC		0.42
ClinPred		0.0045	T
GERP RS		2.2
Varity_R		0.063
gMVP		0.61
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

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