dbSNP rs1963773525: NOMO1:p.Pro211Thr (chr16-14852478-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014287.4(NOMO1):c.631C>A(p.Pro211Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000744 in 1,344,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P211S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

NOMO1
NM_014287.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95

Publications

0 publications found

Variant links:

Genes affected

NOMO1 (HGNC:30060): (NODAL modulator 1) 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 region of duplication located on the p 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 (PXE). [provided by RefSeq, Jul 2008]

NOMO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19402859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014287.4. 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
	NOMO1	NM_014287.4	MANE Select	c.631C>A	p.Pro211Thr	missense	Exon 7 of 31	NP_055102.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOMO1	ENST00000287667.12	TSL:1 MANE Select	c.631C>A	p.Pro211Thr	missense	Exon 7 of 31	ENSP00000287667.7	Q15155
NOMO1	ENST00000880310.1		c.631C>A	p.Pro211Thr	missense	Exon 7 of 31	ENSP00000550369.1
NOMO1	ENST00000924494.1		c.631C>A	p.Pro211Thr	missense	Exon 7 of 31	ENSP00000594553.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.44e-7

AC:

AN:

1344470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

660866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29814

American (AMR)

AF:

0.00

AC:

AN:

28800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21746

East Asian (EAS)

AF:

0.0000269

AC:

AN:

37186

South Asian (SAS)

AF:

0.00

AC:

AN:

72930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1045764

Other (OTH)

AF:

0.00

AC:

AN:

55524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-0.055

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0057

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

PhyloP100

4.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.17

Polyphen

0.65

Vest4

0.32

MutPred

0.48

Gain of sheet (P = 0.0043)

MVP

0.28

ClinPred

0.64

GERP RS

2.8

Varity_R

0.098

gMVP

0.33

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over