16-14853543-C-T

Variant names:

• chr16-14853543-C-T
• rs549552033
• NM_014287.4:c.812C>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.812C>T​(p.Thr271Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,608,002 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 19)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: NOMO1 NM_014287.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• 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=0.036330163).

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.812C>T	p.Thr271Met	missense	Exon 8 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.812C>T	p.Thr271Met	missense	Exon 8 of 31	ENSP00000287667.7	Q15155
	NOMO1	ENST00000880310.1		c.812C>T	p.Thr271Met	missense	Exon 8 of 31	ENSP00000550369.1
	NOMO1	ENST00000924494.1		c.812C>T	p.Thr271Met	missense	Exon 8 of 31	ENSP00000594553.1

Frequencies

GnomAD3 genomes AF: 0.000249 AC: 37 AN: 148352 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000217

Gnomad FIN AF: 0.0000979

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000460

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000251 AC: 63 AN: 250540 AF XY: 0.000244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000442

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000280 AC: 409 AN: 1459540 Hom.: 1 Cov.: 31 AF XY: 0.000306 AC XY: 222 AN XY: 726076

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.0000671 AC: 3 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86144

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.000325 AC: 361 AN: 1111734

Other (OTH) AF: 0.000233 AC: 14 AN: 60198

GnomAD4 genome AF: 0.000249 AC: 37 AN: 148462 Hom.: 0 Cov.: 19 AF XY: 0.000235 AC XY: 17 AN XY: 72270

African (AFR) AF: 0.00 AC: 0 AN: 39754

American (AMR) AF: 0.000269 AC: 4 AN: 14856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 4992

South Asian (SAS) AF: 0.000217 AC: 1 AN: 4602

European-Finnish (FIN) AF: 0.0000979 AC: 1 AN: 10212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000460 AC: 31 AN: 67354

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.000305 AC: 37

EpiCase AF: 0.000763

EpiControl AF: 0.000356

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	0.075
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.028
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.023	D
Polyphen		0.53	P
Vest4		0.13
MVP		0.15
ClinPred		0.024	T
GERP RS		1.0
Varity_R		0.019
gMVP		0.44
Mutation Taster		=91/9	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: rs549552033; hg19: chr16-14947400;