16-14857264-C-T

Variant names:

• chr16-14857264-C-T
• rs150296833
• NM_014287.4:c.1011C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014287.4(NOMO1):​c.1011C>T​(p.Asn337Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 150,012 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (22 hom., cov: 29)
  • Exomes 𝑓: 0.00095 (24 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOMO1 NM_014287.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.407
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 16-14857264-C-T is Benign according to our data. Variant chr16-14857264-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 710343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.407 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00865 (1297/150012) while in subpopulation AFR AF = 0.0299 (1201/40128). AF 95% confidence interval is 0.0285. There are 22 homozygotes in GnomAd4. There are 614 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

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.1011C>T	p.Asn337Asn	synonymous	Exon 10 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.1011C>T	p.Asn337Asn	synonymous	Exon 10 of 31	ENSP00000287667.7	Q15155
	NOMO1	ENST00000880310.1		c.1011C>T	p.Asn337Asn	synonymous	Exon 10 of 31	ENSP00000550369.1
	NOMO1	ENST00000924494.1		c.1011C>T	p.Asn337Asn	synonymous	Exon 10 of 31	ENSP00000594553.1

Frequencies

GnomAD3 genomes AF: 0.00863 AC: 1294 AN: 149900 Hom.: 22 Cov.: 29

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.000975

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00439

GnomAD2 exomes AF: 0.00275 AC: 376 AN: 136728 AF XY: 0.00214

Gnomad AFR exome AF: 0.0365

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.00203

Gnomad EAS exome AF: 0.000809

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.000266

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000952 AC: 1384 AN: 1454126 Hom.: 24 Cov.: 30 AF XY: 0.000865 AC XY: 626 AN XY: 723780

African (AFR) AF: 0.0298 AC: 985 AN: 33076

American (AMR) AF: 0.00233 AC: 104 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26082

East Asian (EAS) AF: 0.000379 AC: 15 AN: 39572

South Asian (SAS) AF: 0.000151 AC: 13 AN: 85914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5742

European-Non Finnish (NFE) AF: 0.0000633 AC: 70 AN: 1105908

Other (OTH) AF: 0.00233 AC: 140 AN: 60038

GnomAD4 genome AF: 0.00865 AC: 1297 AN: 150012 Hom.: 22 Cov.: 29 AF XY: 0.00838 AC XY: 614 AN XY: 73290

African (AFR) AF: 0.0299 AC: 1201 AN: 40128

American (AMR) AF: 0.00451 AC: 68 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 5 AN: 3458

East Asian (EAS) AF: 0.000978 AC: 5 AN: 5114

South Asian (SAS) AF: 0.000424 AC: 2 AN: 4712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000886 AC: 6 AN: 67750

Other (OTH) AF: 0.00435 AC: 9 AN: 2070

Alfa AF: 0.00190 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.81
DANN	Benign	0.49
PhyloP100		-0.41
Mutation Taster		=100/0	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: rs150296833; hg19: chr16-14951121;