rs569206705
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001982.4(ERBB3):c.394C>G(p.Arg132Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Consequence
ERBB3
NM_001982.4 missense
NM_001982.4 missense
Scores
4
12
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.05
Genes affected
ERBB3 (HGNC:3431): (erb-b2 receptor tyrosine kinase 3) This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the ERBB3 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 13 curated pathogenic missense variants (we use a threshold of 10). The gene has 12 curated benign missense variants. Gene score misZ: 1.3904 (below the threshold of 3.09). Trascript score misZ: 3.2897 (above the threshold of 3.09). GenCC associations: The gene is linked to Hirschsprung disease, lethal congenital contracture syndrome 2.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.88
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERBB3 | NM_001982.4 | c.394C>G | p.Arg132Gly | missense_variant | Exon 3 of 28 | ENST00000267101.8 | NP_001973.2 | |
ERBB3 | NM_001005915.1 | c.394C>G | p.Arg132Gly | missense_variant | Exon 3 of 3 | NP_001005915.1 | ||
ERBB3 | XM_047428500.1 | c.217C>G | p.Arg73Gly | missense_variant | Exon 3 of 28 | XP_047284456.1 | ||
ERBB3 | XM_047428501.1 | c.217C>G | p.Arg73Gly | missense_variant | Exon 3 of 28 | XP_047284457.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;M;.;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.29, 0.98
.;B;D;.;.
Vest4
0.59, 0.44, 0.62
MutPred
0.74
.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;.;
MVP
MPC
0.96
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.