16-16232681-G-T

Variant names:

• chr16-16232681-G-T
• NM_001004067.4:c.15G>T
• NOMO3 p.Gln5His

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004067.4(NOMO3):​c.15G>T​(p.Gln5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 19)
• Consequence: NOMO3 NM_001004067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.089146346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004067.4. 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
	NOMO3	NM_001004067.4	MANE Select	c.15G>T	p.Gln5His	missense	Exon 1 of 31	NP_001004067.1	P69849

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOMO3	ENST00000399336.9	TSL:1 MANE Select	c.15G>T	p.Gln5His	missense	Exon 1 of 31	ENSP00000382274.4	P69849
	NOMO3	ENST00000263012.10	TSL:1	c.15G>T	p.Gln5His	missense	Exon 1 of 32	ENSP00000263012.6	J3KN36
	NOMO3	ENST00000575225.5	TSL:1	n.15G>T		non_coding_transcript_exon	Exon 1 of 31	ENSP00000458267.1	I3L0Q6

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.049
Sift	Benign	0.17	T
Sift4G	Benign	0.17	T
PromoterAI		0.22	Neutral
Varity_R		0.069
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-16326538;