chr16-14852478-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014287.4(NOMO1):​c.631C>T​(p.Pro211Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

NOMO1
NM_014287.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1173667).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOMO1NM_014287.4 linkc.631C>T p.Pro211Ser missense_variant Exon 7 of 31 ENST00000287667.12 NP_055102.3 Q15155

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOMO1ENST00000287667.12 linkc.631C>T p.Pro211Ser missense_variant Exon 7 of 31 1 NM_014287.4 ENSP00000287667.7 Q15155
NOMO1ENST00000566720.5 linkn.306C>T non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
25
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.631C>T (p.P211S) alteration is located in exon 7 (coding exon 7) of the NOMO1 gene. This alteration results from a C to T substitution at nucleotide position 631, causing the proline (P) at amino acid position 211 to be replaced by a serine (S). 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
0.076
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.0022
T;T;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.3
L;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.11
N;.;.
REVEL
Benign
0.091
Sift
Benign
0.45
T;.;.
Sift4G
Benign
0.39
T;T;T
Polyphen
0.28
B;.;.
Vest4
0.19
MVP
0.24
ClinPred
0.61
D
GERP RS
2.8
Varity_R
0.047
gMVP
0.30

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: rs1963773525; hg19: chr16-14946335; API