16-16261533-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004067.4(NOMO3):​c.1252C>T​(p.Arg418Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,447,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 27)
Exomes 𝑓: 0.000011 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NOMO3
NM_001004067.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOMO3NM_001004067.4 linkc.1252C>T p.Arg418Cys missense_variant Exon 12 of 31 ENST00000399336.9 NP_001004067.1 P69849Q1LZN2
NOMO3XM_005255318.2 linkc.1252C>T p.Arg418Cys missense_variant Exon 12 of 32 XP_005255375.1 J3KN36

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOMO3ENST00000399336.9 linkc.1252C>T p.Arg418Cys missense_variant Exon 12 of 31 1 NM_001004067.4 ENSP00000382274.4 P69849

Frequencies

GnomAD3 genomes
AF:
0.00000710
AC:
1
AN:
140888
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000302
AC:
6
AN:
198726
Hom.:
1
AF XY:
0.0000370
AC XY:
4
AN XY:
107996
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000626
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000111
AC:
16
AN:
1447370
Hom.:
0
Cov.:
30
AF XY:
0.0000125
AC XY:
9
AN XY:
720126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000710
AC:
1
AN:
140888
Hom.:
0
Cov.:
27
AF XY:
0.0000146
AC XY:
1
AN XY:
68504
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000337
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1252C>T (p.R418C) alteration is located in exon 12 (coding exon 12) of the NOMO3 gene. This alteration results from a C to T substitution at nucleotide position 1252, causing the arginine (R) at amino acid position 418 to be replaced by a cysteine (C). 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
0.13
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.032
T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.098
D
MetaRNN
Uncertain
0.60
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.2
N;N
REVEL
Benign
0.24
Sift
Benign
0.046
D;D
Sift4G
Uncertain
0.031
D;D
Polyphen
1.0
D;.
Vest4
0.54
MutPred
0.63
Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);
MVP
0.41
ClinPred
0.61
D
GERP RS
3.8
Varity_R
0.19
gMVP
0.57

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.

Other links and lift over

dbSNP: rs765377766; hg19: chr16-16355390; API