11-131911534-C-G

Variant names:

• chr11-131911534-C-G
• rs376930803
• ENST00000425719.6:c.53C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001352005.2(NTM):​c.83-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,614,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: NTM NM_001352005.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• 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]

ENSG00000294035 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030322999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTM	NM_001352005.2	c.83-30C>G		intron_variant	Intron 1 of 8	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.83-30C>G		intron_variant	Intron 1 of 8		NM_001352005.2	ENSP00000507313.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 251336 AF XY: 0.000169

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000122 AC: 179 AN: 1461866 Hom.: 1 Cov.: 32 AF XY: 0.000120 AC XY: 87 AN XY: 727230

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000470 AC: 21 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000110 AC: 122 AN: 1111988

Other (OTH) AF: 0.000480 AC: 29 AN: 60394

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74486

African (AFR) AF: 0.000120 AC: 5 AN: 41586

American (AMR) AF: 0.000653 AC: 10 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000310

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000350 AC: 3

ExAC AF: 0.000148 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53C>G (p.S18C) alteration is located in exon 1 (coding exon 1) of the NTM gene. This alteration results from a C to G substitution at nucleotide position 53, causing the serine (S) at amino acid position 18 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.0063	T;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.030	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;N;N
PhyloP100		3.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.081
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.17
MVP		0.45
MPC		1.7
ClinPred		0.022	T
GERP RS		4.3
PromoterAI		-0.0043	Neutral
Varity_R		0.18
gMVP		0.41
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs376930803; hg19: chr11-131781428;