rs1057519893
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001982.4(ERBB3):c.310G>A(p.Val104Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V104L) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ERBB3
NM_001982.4 missense
NM_001982.4 missense
Scores
1
13
4
Clinical Significance
Conservation
PhyloP100: 4.31
Publications
98 publications found
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]
ERBB3 Gene-Disease associations (from GenCC):
- lethal congenital contracture syndrome 2Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- visceral neuropathy, familial, 1, autosomal recessiveInheritance: AR Classification: STRONG Submitted by: G2P
- Hirschsprung diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.824
PP5
Variant 12-56085070-G-A is Pathogenic according to our data. Variant chr12-56085070-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 376410.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001982.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ERBB3 | NM_001982.4 | MANE Select | c.310G>A | p.Val104Met | missense | Exon 3 of 28 | NP_001973.2 | ||
| ERBB3 | NM_001005915.1 | c.310G>A | p.Val104Met | missense | Exon 3 of 3 | NP_001005915.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ERBB3 | ENST00000267101.8 | TSL:1 MANE Select | c.310G>A | p.Val104Met | missense | Exon 3 of 28 | ENSP00000267101.4 | ||
| ERBB3 | ENST00000411731.6 | TSL:1 | c.310G>A | p.Val104Met | missense | Exon 3 of 3 | ENSP00000415753.2 | ||
| ERBB3 | ENST00000551242.5 | TSL:1 | n.310G>A | non_coding_transcript_exon | Exon 3 of 11 | ENSP00000447510.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727248 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461894
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727248
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided