dbSNP rs891784012: NOMO3:p.Thr16Ile (chr16-16232713-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOMO3	NM_001004067.4	MANE Select	c.47C>T	p.Thr16Ile	missense	Exon 1 of 31	NP_001004067.1	P69849

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOMO3	ENST00000399336.9	TSL:1 MANE Select	c.47C>T	p.Thr16Ile	missense	Exon 1 of 31	ENSP00000382274.4	P69849
NOMO3	ENST00000263012.10	TSL:1	c.47C>T	p.Thr16Ile	missense	Exon 1 of 32	ENSP00000263012.6	J3KN36
NOMO3	ENST00000575225.5	TSL:1	n.47C>T		non_coding_transcript_exon	Exon 1 of 31	ENSP00000458267.1	I3L0Q6

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

African (AFR)

AF:

0.00

AC:

AN:

13750

American (AMR)

AF:

0.000141

AC:

AN:

7106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10518

East Asian (EAS)

AF:

0.00

AC:

AN:

22254

South Asian (SAS)

AF:

0.00

AC:

AN:

14136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21642

Middle Eastern (MID)

AF:

0.000483

AC:

AN:

2070

European-Non Finnish (NFE)

AF:

0.0000465

AC:

AN:

516654

Other (OTH)

AF:

0.0000348

AC:

AN:

28708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000530

AC:

AN:

132098

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

63618

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33994

American (AMR)

AF:

0.000225

AC:

AN:

13326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3222

East Asian (EAS)

AF:

0.00

AC:

AN:

4254

South Asian (SAS)

AF:

0.00

AC:

AN:

3744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000644

AC:

AN:

62066

Other (OTH)

AF:

0.00

AC:

AN:

1674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.589

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000169

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.4

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0032

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.54

M_CAP

Benign

0.012

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

PhyloP100

-0.40

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.47

REVEL

Benign

0.023

Sift

Benign

0.30

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.11

MutPred

0.43

Loss of glycosylation at T16 (P = 0.0312)

MVP

0.072

ClinPred

0.049

GERP RS

-0.091

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.046

gMVP

0.11

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over