16-16261592-C-A

Variant names:

• chr16-16261592-C-A
• rs770450328
• NM_001004067.4:c.1311C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004067.4(NOMO3):​c.1311C>A​(p.Asp437Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NOMO3 NM_001004067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06486896).

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.1311C>A	p.Asp437Glu	missense	Exon 12 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.1311C>A	p.Asp437Glu	missense	Exon 12 of 31	ENSP00000382274.4	P69849
	NOMO3	ENST00000263012.10	TSL:1	c.1311C>A	p.Asp437Glu	missense	Exon 12 of 32	ENSP00000263012.6	J3KN36
	NOMO3	ENST00000575225.5	TSL:1	n.*787C>A		non_coding_transcript_exon	Exon 11 of 31	ENSP00000458267.1	I3L0Q6

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.00000461 AC: 1 AN: 217114 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: 0.00000964

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442514 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717660

African (AFR) AF: 0.00 AC: 0 AN: 29084

American (AMR) AF: 0.00 AC: 0 AN: 43004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25854

East Asian (EAS) AF: 0.00 AC: 0 AN: 36228

South Asian (SAS) AF: 0.00 AC: 0 AN: 83926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4076

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107670

Other (OTH) AF: 0.00 AC: 0 AN: 59306

GnomAD4 genome Cov.: 27

ExAC AF: 0.00000857 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.70
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.039
Sift	Benign	0.23	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.060
MutPred		0.37		Loss of sheet (P = 0.0357)
MVP		0.20
ClinPred		0.083	T
GERP RS		1.4
Varity_R		0.048
gMVP		0.29

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

Other links and lift over

dbSNP: rs770450328; hg19: chr16-16355449;