Genetic Variant NOMO3:p.Gln5His (chr16-16232681-G-C) – 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.15G>C(p.Gln5His) 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 0.000044 ( 0 hom., cov: 19)

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: 1.72

Publications

0 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:

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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=0.08682352).

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.15G>C	p.Gln5His	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.15G>C	p.Gln5His	missense	Exon 1 of 31	ENSP00000382274.4	P69849
NOMO3	ENST00000263012.10	TSL:1	c.15G>C	p.Gln5His	missense	Exon 1 of 32	ENSP00000263012.6	J3KN36
NOMO3	ENST00000575225.5	TSL:1	n.15G>C		non_coding_transcript_exon	Exon 1 of 31	ENSP00000458267.1	I3L0Q6

Frequencies

GnomAD3 genomes

AF:

0.0000443

AC:

AN:

135566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000570

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000110

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000474

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000422

AC:

AN:

734160

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

352998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15678

American (AMR)

AF:

0.00

AC:

AN:

7096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10904

East Asian (EAS)

AF:

0.00

AC:

AN:

22392

South Asian (SAS)

AF:

0.00

AC:

AN:

15072

European-Finnish (FIN)

AF:

0.0000474

AC:

AN:

21102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2190

European-Non Finnish (NFE)

AF:

0.0000493

AC:

AN:

608274

Other (OTH)

AF:

0.00

AC:

AN:

31452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000443

AC:

AN:

135566

Hom.:

Cov.:

AF XY:

0.0000459

AC XY:

AN XY:

65316

show subpopulations

African (AFR)

AF:

0.0000570

AC:

AN:

35078

American (AMR)

AF:

0.00

AC:

AN:

13674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3266

East Asian (EAS)

AF:

0.00

AC:

AN:

4364

South Asian (SAS)

AF:

0.00

AC:

AN:

3862

European-Finnish (FIN)

AF:

0.000110

AC:

AN:

9122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000474

AC:

AN:

63330

Other (OTH)

AF:

0.00

AC:

AN:

1768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000712

Hom.:

Bravo

AF:

0.0000189

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

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0025

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.51

M_CAP

Benign

0.040

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

PhyloP100

1.7

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.32

REVEL

Benign

0.049

Sift

Benign

0.17

Sift4G

Benign

0.17

Polyphen

0.025

Vest4

0.039

MutPred

0.16

Loss of catalytic residue at Q5 (P = 0.0502)

MVP

0.14

ClinPred

0.063

GERP RS

2.9

PromoterAI

0.026

Neutral

(source)

Varity_R

0.069

gMVP

0.33

Mutation Taster

=85/15

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