Genetic Variant NOMO1:c.302-3C>T (chr16-14844671-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014287.4(NOMO1):c.302-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000082 ( 0 hom., cov: 13)

Exomes 𝑓: 0.00029 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

NOMO1
NM_014287.4 splice_region, intron

Scores

Splicing: ADA: 0.0007105

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52

Variant links:

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]

NOMO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 16-14844671-C-T is Benign according to our data. Variant chr16-14844671-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646241.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOMO1	NM_014287.4 link	c.302-3C>T		splice_region_variant, intron_variant	Intron 3 of 30	ENST00000287667.12	NP_055102.3	Q15155

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOMO1	ENST00000287667.12 link	c.302-3C>T		splice_region_variant, intron_variant	Intron 3 of 30	1	NM_014287.4	ENSP00000287667.7		Q15155

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

109854

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00232

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000522

AC:

AN:

15314

Hom.:

AF XY:

0.000595

AC XY:

AN XY:

8400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00227

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00188

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000295

AC:

140

AN:

474836

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

105

AN XY:

246718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00318

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000344

Gnomad4 OTH exome

AF:

0.000190

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000819

AC:

AN:

109912

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

50330

show subpopulations

Gnomad4 AFR

AF:

0.000105

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00233

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NOMO1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00071

dbscSNV1_RF

Benign

0.086

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over