chr16-14852478-C-T

Variant names:

• chr16-14852478-C-T
• rs1963773525
• NM_014287.4:c.631C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

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]

ACMG classification

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
NOMO1	NM_014287.4	c.631C>T	p.Pro211Ser	missense_variant	Exon 7 of 31	ENST00000287667.12	NP_055102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOMO1	ENST00000287667.12	c.631C>T	p.Pro211Ser	missense_variant	Exon 7 of 31	1	NM_014287.4	ENSP00000287667.7
NOMO1	ENST00000566720.5	n.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

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

Other links and lift over

dbSNP: rs1963773525; hg19: chr16-14946335;