Genetic Variant NM_014287.4:c.674G>A (chr16-14852521-G-A) – 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_014287.4(NOMO1):c.674G>A(p.Ser225Asn) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOMO1
NM_014287.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.57

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:

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=0.22050226).

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.674G>A	p.Ser225Asn	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.674G>A	p.Ser225Asn	missense	Exon 7 of 31	ENSP00000287667.7	Q15155
NOMO1	ENST00000880310.1		c.674G>A	p.Ser225Asn	missense	Exon 7 of 31	ENSP00000550369.1
NOMO1	ENST00000924494.1		c.674G>A	p.Ser225Asn	missense	Exon 7 of 31	ENSP00000594553.1

Frequencies

GnomAD3 genomes

AF:

0.0000683

AC:

AN:

146308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000180

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000452

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

36028

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00168

AC:

2256

AN:

1344542

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1084

AN XY:

667698

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00281

AC:

AN:

29520

American (AMR)

AF:

0.000451

AC:

AN:

35448

Ashkenazi Jewish (ASJ)

AF:

0.000810

AC:

AN:

23464

East Asian (EAS)

AF:

0.0000516

AC:

AN:

38754

South Asian (SAS)

AF:

0.000607

AC:

AN:

79090

European-Finnish (FIN)

AF:

0.000589

AC:

AN:

50962

Middle Eastern (MID)

AF:

0.000264

AC:

AN:

3790

European-Non Finnish (NFE)

AF:

0.00193

AC:

1985

AN:

1027644

Other (OTH)

AF:

0.00129

AC:

AN:

55870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.251

Heterozygous variant carriers

312

624

935

1247

1559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

204

306

408

510

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000683

AC:

AN:

146308

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

71110

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000180

AC:

AN:

38982

American (AMR)

AF:

0.00

AC:

AN:

14680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5016

South Asian (SAS)

AF:

0.00

AC:

AN:

4504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000452

AC:

AN:

66302

Other (OTH)

AF:

0.00

AC:

AN:

1966

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.235

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:

0.00

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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-0.019

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Benign

0.0096

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

PhyloP100

8.6

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.050

Polyphen

0.24

Vest4

0.38

MVP

0.25

ClinPred

0.97

GERP RS

2.8

Varity_R

0.45

gMVP

0.57

Mutation Taster

=61/39

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