chr16-14846618-G-A

Variant names:

• chr16-14846618-G-A
• rs568175211
• NM_014287.4:c.444G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_014287.4(NOMO1):​c.444G>A​(p.Gln148Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 19)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOMO1 NM_014287.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.

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.444G>A	p.Gln148Gln	synonymous	Exon 5 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.444G>A	p.Gln148Gln	synonymous	Exon 5 of 31	ENSP00000287667.7	Q15155
	NOMO1	ENST00000880310.1		c.444G>A	p.Gln148Gln	synonymous	Exon 5 of 31	ENSP00000550369.1
	NOMO1	ENST00000924494.1		c.444G>A	p.Gln148Gln	synonymous	Exon 5 of 31	ENSP00000594553.1

Frequencies

GnomAD3 genomes AF: 0.0000221 AC: 3 AN: 135574 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000529 AC: 1 AN: 189182 AF XY: 0.00000978

Gnomad AFR exome AF: 0.0000898

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.34e-7 AC: 1 AN: 1198812 Hom.: 0 Cov.: 16 AF XY: 0.00000167 AC XY: 1 AN XY: 600532

African (AFR) AF: 0.0000359 AC: 1 AN: 27838

American (AMR) AF: 0.00 AC: 0 AN: 37162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22480

East Asian (EAS) AF: 0.00 AC: 0 AN: 36926

South Asian (SAS) AF: 0.00 AC: 0 AN: 74404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 894750

Other (OTH) AF: 0.00 AC: 0 AN: 51276

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000221 AC: 3 AN: 135690 Hom.: 0 Cov.: 19 AF XY: 0.0000308 AC XY: 2 AN XY: 65028

African (AFR) AF: 0.0000861 AC: 3 AN: 34838

American (AMR) AF: 0.00 AC: 0 AN: 13194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3274

East Asian (EAS) AF: 0.00 AC: 0 AN: 4652

South Asian (SAS) AF: 0.00 AC: 0 AN: 3736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63898

Other (OTH) AF: 0.00 AC: 0 AN: 1752

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.0
DANN	Benign	0.70
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs568175211; hg19: chr16-14940475;