16-16261629-C-T

Variant names:

• chr16-16261629-C-T
• NM_001004067.4:c.1348C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004067.4(NOMO3):​c.1348C>T​(p.His450Tyr) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000021 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOMO3 NM_001004067.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31531203).

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.1348C>T	p.His450Tyr	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.1348C>T	p.His450Tyr	missense	Exon 12 of 31	ENSP00000382274.4	P69849
	NOMO3	ENST00000263012.10	TSL:1	c.1348C>T	p.His450Tyr	missense	Exon 12 of 32	ENSP00000263012.6	J3KN36
	NOMO3	ENST00000575225.5	TSL:1	n.*824C>T		non_coding_transcript_exon	Exon 11 of 31	ENSP00000458267.1	I3L0Q6

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000208 AC: 3 AN: 1443748 Hom.: 1 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 718314

African (AFR) AF: 0.000103 AC: 3 AN: 29216

American (AMR) AF: 0.00 AC: 0 AN: 43908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 36178

South Asian (SAS) AF: 0.00 AC: 0 AN: 84544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4088

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107254

Other (OTH) AF: 0.00 AC: 0 AN: 59314

GnomAD4 genome Cov.: 27

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	0.081
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.026
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.063	T
Sift4G	Benign	0.070	T
Polyphen		0.23	B
Vest4		0.33
MutPred		0.50		Gain of phosphorylation at H450 (P = 0.0195)
MVP		0.21
ClinPred		0.93	D
GERP RS		3.8
Varity_R		0.12
gMVP		0.21
Mutation Taster		=64/36	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

hg19: chr16-16355486;