NM_003502.4:c.2403G>C

Variant names:

• chr16-289499-C-G
• rs113073289
• NM_003502.4:c.2403G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003502.4(AXIN1):​c.2403G>C​(p.Arg801Ser) 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. 14/22 in silico tools predict 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. R801R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AXIN1 NM_003502.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 6 publications found

Genes affected

AXIN1 (HGNC:903): (axin 1) This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 beta, protein phosphate 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

AXIN1 Gene-Disease associations (from GenCC):

• caudal duplication

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1711447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.2403G>C	p.Arg801Ser	missense_variant	Exon 10 of 11	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.2403G>C	p.Arg801Ser	missense_variant	Exon 10 of 11	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.2295G>C	p.Arg765Ser	missense_variant	Exon 9 of 10	1		ENSP00000346935.3
AXIN1	ENST00000457798.1	c.156G>C	p.Arg52Ser	missense_variant	Exon 2 of 3	3		ENSP00000416835.1
AXIN1	ENST00000461023.5	n.5472G>C		non_coding_transcript_exon_variant	Exon 7 of 8	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N;.
PhyloP100		0.16
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.12
Sift	Benign	0.040	D;D
Sift4G	Benign	0.21	T;T
Polyphen		0.88	P;B
Vest4		0.35
MutPred		0.64		Loss of methylation at R801 (P = 0.0352);.;
MVP		0.27
MPC		0.74
ClinPred		0.88	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.50
gMVP		0.56
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs113073289; hg19: chr16-339499;