rs77151171
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018055.5(NODAL):c.357C>T(p.Pro119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,614,104 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00087 ( 11 hom. )
Consequence
NODAL
NM_018055.5 synonymous
NM_018055.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.01
Genes affected
NODAL (HGNC:7865): (nodal growth differentiation factor) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which regulates early embryonic development. This protein is required for maintenance of human embryonic stem cell pluripotency and may play a role in human placental development. Mutations in this gene are associated with heterotaxy, a condition characterized by random orientation of visceral organs with respect to the left-right axis. [provided by RefSeq, Aug 2016]
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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=-0.85).
BP6
?
Variant 10-70435820-G-A is Benign according to our data. Variant chr10-70435820-G-A is described in ClinVar as [Benign]. Clinvar id is 300305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=-2.01 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000624 (95/152320) while in subpopulation SAS AF= 0.00643 (31/4824). AF 95% confidence interval is 0.00465. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 95 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NODAL | NM_018055.5 | c.357C>T | p.Pro119= | synonymous_variant | 2/3 | ENST00000287139.8 | |
NODAL | NM_001329906.2 | c.-43C>T | 5_prime_UTR_variant | 2/3 | |||
NODAL | XM_024448028.2 | c.-43C>T | 5_prime_UTR_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NODAL | ENST00000287139.8 | c.357C>T | p.Pro119= | synonymous_variant | 2/3 | 1 | NM_018055.5 | P1 | |
NODAL | ENST00000414871.1 | c.192C>T | p.Pro64= | synonymous_variant | 2/3 | 1 | |||
ENST00000624563.1 | n.992G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00111 AC: 278AN: 250830Hom.: 1 AF XY: 0.00151 AC XY: 205AN XY: 135772
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GnomAD4 exome AF: 0.000865 AC: 1265AN: 1461784Hom.: 11 Cov.: 34 AF XY: 0.00109 AC XY: 791AN XY: 727190
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GnomAD4 genome ? AF: 0.000624 AC: 95AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Heterotaxy, visceral, 5, autosomal Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 23, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Holoprosencephaly sequence Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at