16-14857264-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOMO1	NM_014287.4	c.1011C>T	p.Asn337Asn	synonymous_variant	Exon 10 of 31	ENST00000287667.12	NP_055102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOMO1	ENST00000287667.12	c.1011C>T	p.Asn337Asn	synonymous_variant	Exon 10 of 31	1	NM_014287.4	ENSP00000287667.7
NOMO1	ENST00000566883.5	n.303C>T		non_coding_transcript_exon_variant	Exon 4 of 6	4
NOMO1	ENST00000566917.1	n.487C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2

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

GnomAD3 exomes AF: 0.00275 AC: 376 AN: 136728 Hom.: 9 AF XY: 0.00214 AC XY: 155 AN XY: 72292

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 SAS exome AF: 0.000273

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

Gnomad4 AFR exome AF: 0.0298

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.000379

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000633

Gnomad4 OTH exome AF: 0.00233

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

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00145

Gnomad4 EAS AF: 0.000978

Gnomad4 SAS AF: 0.000424

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.00435

Alfa AF: 0.00190 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.81
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs150296833; hg19: chr16-14951121;