10-70435307-C-G

Variant names:

• chr10-70435307-C-G
• rs763525961
• NM_018055.5:c.870G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018055.5(NODAL):​c.870G>C​(p.Pro290Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P290P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NODAL NM_018055.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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]

ENSG00000280401 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-2.72 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NODAL	NM_018055.5	c.870G>C	p.Pro290Pro	synonymous_variant	Exon 2 of 3	ENST00000287139.8	NP_060525.3
NODAL	NM_001329906.2	c.471G>C	p.Pro157Pro	synonymous_variant	Exon 2 of 3		NP_001316835.1
NODAL	XM_024448028.2	c.471G>C	p.Pro157Pro	synonymous_variant	Exon 2 of 3		XP_024303796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NODAL	ENST00000287139.8	c.870G>C	p.Pro290Pro	synonymous_variant	Exon 2 of 3	1	NM_018055.5	ENSP00000287139.3
NODAL	ENST00000414871.1	c.705G>C	p.Pro235Pro	synonymous_variant	Exon 2 of 3	1		ENSP00000394468.1
ENSG00000280401	ENST00000624563.1	n.479C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247072 Hom.: 0 AF XY: 0.00000749 AC XY: 1 AN XY: 133496

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: 0.0000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.082
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs763525961; hg19: chr10-72195063;