16-14853988-C-T

Variant names:

• chr16-14853988-C-T
• rs533739263
• NM_014287.4:c.925C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014287.4(NOMO1):​c.925C>T​(p.Leu309Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOMO1 NM_014287.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009767175).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014287.4. 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
	NOMO1	NM_014287.4	MANE Select	c.925C>T	p.Leu309Phe	missense	Exon 9 of 31	NP_055102.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOMO1	ENST00000287667.12	TSL:1 MANE Select	c.925C>T	p.Leu309Phe	missense	Exon 9 of 31	ENSP00000287667.7	Q15155
	NOMO1	ENST00000880310.1		c.925C>T	p.Leu309Phe	missense	Exon 9 of 31	ENSP00000550369.1
	NOMO1	ENST00000924494.1		c.925C>T	p.Leu309Phe	missense	Exon 9 of 31	ENSP00000594553.1

Frequencies

GnomAD3 genomes AF: 0.0000406 AC: 6 AN: 147608 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000406

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000210 AC: 17 AN: 80984 AF XY: 0.000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000437

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000213 AC: 31 AN: 1457508 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 725246

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.000649 AC: 29 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110066

Other (OTH) AF: 0.0000333 AC: 2 AN: 60148

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000406 AC: 6 AN: 147712 Hom.: 0 Cov.: 19 AF XY: 0.0000279 AC XY: 2 AN XY: 71812

African (AFR) AF: 0.00 AC: 0 AN: 39548

American (AMR) AF: 0.000406 AC: 6 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.00 AC: 0 AN: 4590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66916

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.0000744 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000337 AC: 6

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	0.19
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.079
Sift	Benign	0.11	T
Sift4G	Uncertain	0.014	D
Polyphen		0.96	D
Vest4		0.25
MutPred		0.44		Loss of stability (P = 0.1364)
MVP		0.27
ClinPred		0.19	T
GERP RS		2.8
Varity_R		0.11
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

Other links and lift over

dbSNP: rs533739263; hg19: chr16-14947845;