chr16-16255805-C-T

Variant names:

• chr16-16255805-C-T
• rs374363601
• NM_001004067.4:c.1049C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001004067.4(NOMO3):​c.1049C>T​(p.Thr350Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,561,404 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (1 hom., cov: 20)
  • Exomes 𝑓: 0.00011 (5 hom.)
• Consequence: NOMO3 NM_001004067.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08055177).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

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.1049C>T	p.Thr350Ile	missense	Exon 10 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.1049C>T	p.Thr350Ile	missense	Exon 10 of 31	ENSP00000382274.4	P69849
	NOMO3	ENST00000263012.10	TSL:1	c.1049C>T	p.Thr350Ile	missense	Exon 10 of 32	ENSP00000263012.6	J3KN36
	NOMO3	ENST00000575225.5	TSL:1	n.*525C>T		non_coding_transcript_exon	Exon 9 of 31	ENSP00000458267.1	I3L0Q6

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 19 AN: 125348 Hom.: 1 Cov.: 20

Gnomad AFR AF: 0.0000776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000232

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: 0.000204

Gnomad OTH AF: 0.000588

GnomAD2 exomes AF: 0.000127 AC: 31 AN: 244168 AF XY: 0.000151

Gnomad AFR exome AF: 0.0000720

Gnomad AMR exome AF: 0.0000590

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000232

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000111 AC: 160 AN: 1436014 Hom.: 5 Cov.: 30 AF XY: 0.000116 AC XY: 83 AN XY: 714930

African (AFR) AF: 0.000104 AC: 3 AN: 28710

American (AMR) AF: 0.000114 AC: 5 AN: 43942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 35916

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.000130 AC: 143 AN: 1099464

Other (OTH) AF: 0.000136 AC: 8 AN: 59000

GnomAD4 genome AF: 0.000152 AC: 19 AN: 125390 Hom.: 1 Cov.: 20 AF XY: 0.000149 AC XY: 9 AN XY: 60392

African (AFR) AF: 0.0000774 AC: 2 AN: 25838

American (AMR) AF: 0.000232 AC: 3 AN: 12958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3194

East Asian (EAS) AF: 0.00 AC: 0 AN: 3364

South Asian (SAS) AF: 0.00 AC: 0 AN: 3690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.000204 AC: 13 AN: 63868

Other (OTH) AF: 0.000581 AC: 1 AN: 1720

Alfa AF: 0.000192 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.000126 AC: 15

EpiCase AF: 0.000328

EpiControl AF: 0.000238

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N
PhyloP100		3.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.057
Sift	Benign	0.39	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.31
MVP		0.17
ClinPred		0.019	T
GERP RS		2.4
Varity_R		0.053
gMVP		0.17
Mutation Taster		=98/2	polymorphism

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: rs374363601; hg19: chr16-16349662;