Genetic Variant NTM:p.Arg48Arg (chr11-131911625-G-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001352005.2(NTM):c.144G>T(p.Arg48Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,176 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 69 hom. )

Consequence

NTM
NM_001352005.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.33

Publications

2 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:

ENSG00000294035 (HGNC:):

ENSG00000294035 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-131911625-G-T is Benign according to our data. Variant chr11-131911625-G-T is described in ClinVar as [Benign]. Clinvar id is 721283.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00235 (358/152350) while in subpopulation EAS AF = 0.0492 (254/5160). AF 95% confidence interval is 0.0443. There are 5 homozygotes in GnomAd4. There are 177 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTM	NM_001352005.2 link	c.144G>T	p.Arg48Arg	synonymous_variant	Exon 2 of 9	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1 link	c.144G>T	p.Arg48Arg	synonymous_variant	Exon 2 of 9		NM_001352005.2	ENSP00000507313.1		B7Z1Z5

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0491

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00437

AC:

1099

AN:

251328

AF XY:

0.00402

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0487

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000827

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00209

AC:

3051

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1506

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33470

American (AMR)

AF:

0.000425

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0499

AC:

1982

AN:

39700

South Asian (SAS)

AF:

0.00245

AC:

211

AN:

86258

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000468

AC:

520

AN:

1111972

Other (OTH)

AF:

0.00475

AC:

287

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

182

364

546

728

910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00235

AC:

358

AN:

152350

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41598

American (AMR)

AF:

0.000588

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0492

AC:

254

AN:

5160

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000808

AC:

AN:

68040

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000914

Hom.:

Bravo

AF:

0.00249

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

3.3

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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chr11-131911625-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over