Genetic Variant NOMO3:p.Thr16Ile (chr16-16232713-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004067.4(NOMO3):c.47C>T(p.Thr16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

NOMO3
NM_001004067.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.397

Variant links:

Genes affected

NOMO3 (HGNC:25242): (NODAL modulator 3) This gene encodes a protein originally thought to be related to the collagenase gene family. This gene is one of three highly similar genes in a duplicated region on the short arm of chromosome 16. These three genes encode closely related proteins that may have the same function. The protein encoded by one of these genes has been identified as part of a protein complex that participates in the Nodal signaling pathway during vertebrate development. Mutations in ABCC6, which is located nearby, rather than mutations in this gene are associated with pseudoxanthoma elasticum. [provided by RefSeq, Jul 2008]

NOMO3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.069639325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOMO3	NM_001004067.4 link	c.47C>T	p.Thr16Ile	missense_variant	Exon 1 of 31	ENST00000399336.9	NP_001004067.1	P69849Q1LZN2
NOMO3	XM_005255318.2 link	c.47C>T	p.Thr16Ile	missense_variant	Exon 1 of 32		XP_005255375.1	J3KN36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOMO3	ENST00000399336.9 link	c.47C>T	p.Thr16Ile	missense_variant	Exon 1 of 31	1	NM_001004067.4	ENSP00000382274.4		P69849

Frequencies

GnomAD3 genomes

AF:

0.0000530

AC:

AN:

132098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000225

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000644

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000424

AC:

AN:

636838

Hom.:

Cov.:

AF XY:

0.0000356

AC XY:

AN XY:

308636

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000465

Gnomad4 OTH exome

AF:

0.0000348

GnomAD4 genome

AF:

0.0000530

AC:

AN:

132098

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

63618

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000225

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000644

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>T (p.T16I) alteration is located in exon 1 (coding exon 1) of the NOMO3 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the threonine (T) at amino acid position 16 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.4

DANN

Benign

0.96

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

N;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.47

N;N

REVEL

Benign

0.023

Sift

Benign

0.30

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;.

Vest4

0.11

MutPred

0.43

Loss of glycosylation at T16 (P = 0.0312);Loss of glycosylation at T16 (P = 0.0312);

MVP

0.072

ClinPred

0.049

GERP RS

-0.091

Varity_R

0.046

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over