rs104894169

Variant names:

• chr10-70435629-C-G
• NM_018055.5:c.548G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-70435629-C-G
• chr10-70435629-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018055.5(NODAL):​c.548G>C​(p.Arg183Pro) variant causes a missense 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NODAL NM_018055.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13791236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NODAL	NM_018055.5	c.548G>C	p.Arg183Pro	missense_variant	Exon 2 of 3	ENST00000287139.8	NP_060525.3
NODAL	NM_001329906.2	c.149G>C	p.Arg50Pro	missense_variant	Exon 2 of 3		NP_001316835.1
NODAL	XM_024448028.2	c.149G>C	p.Arg50Pro	missense_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.548G>C	p.Arg183Pro	missense_variant	Exon 2 of 3	1	NM_018055.5	ENSP00000287139.3
NODAL	ENST00000414871.1	c.383G>C	p.Arg128Pro	missense_variant	Exon 2 of 3	1		ENSP00000394468.1
ENSG00000280401	ENST00000624563.1	n.801C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.020
DANN	Benign	0.86
DEOGEN2	Uncertain	0.52	D;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.22
Sift	Benign	0.14	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0	B;.
Vest4		0.36
MutPred		0.52		Gain of glycosylation at R183 (P = 0.001);.;
MVP		0.41
MPC		0.45
ClinPred		0.10	T
GERP RS		-8.3
Varity_R		0.17
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-72195385;