chr16-14857264-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.407
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]

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ACMG classification

Classification made for transcript

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
NOMO1NM_014287.4 linkc.1011C>T p.Asn337Asn synonymous_variant Exon 10 of 31 ENST00000287667.12 NP_055102.3 Q15155

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOMO1ENST00000287667.12 linkc.1011C>T p.Asn337Asn synonymous_variant Exon 10 of 31 1 NM_014287.4 ENSP00000287667.7 Q15155
NOMO1ENST00000566883.5 linkn.303C>T non_coding_transcript_exon_variant Exon 4 of 6 4
NOMO1ENST00000566917.1 linkn.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
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

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

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

Other links and lift over

dbSNP: rs150296833; hg19: chr16-14951121; API