rs543098573

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_198722.3(AMIGO3):​c.1248_1256delCCGCCGCTG​(p.Cys416_Arg418del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,612,334 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 6 hom. )

Consequence

AMIGO3
NM_198722.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25
Variant links:
Genes affected
AMIGO3 (HGNC:24075): (adhesion molecule with Ig like domain 3) Predicted to be involved in brain development and heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
RNF123 (HGNC:21148): (ring finger protein 123) The protein encoded by this gene contains a C-terminal RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions, and an N-terminal SPRY domain. This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 or KIP1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
GMPPB (HGNC:22932): (GDP-mannose pyrophosphorylase B) This gene is thought to encode a GDP-mannose pyrophosphorylase. The encoded protein catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, a reaction involved in the production of N-linked oligosaccharides. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_198722.3
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMIGO3NM_198722.3 linkc.1248_1256delCCGCCGCTG p.Cys416_Arg418del disruptive_inframe_deletion Exon 1 of 1 ENST00000320431.8 NP_942015.1 Q86WK7
RNF123NM_022064.5 linkc.3500+1740_3500+1748delGGCAGCGGC intron_variant Intron 35 of 38 ENST00000327697.11 NP_071347.2 Q5XPI4-1
RNF123NR_135218.2 linkn.3826+1740_3826+1748delGGCAGCGGC intron_variant Intron 35 of 38

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMIGO3ENST00000320431.8 linkc.1248_1256delCCGCCGCTG p.Cys416_Arg418del disruptive_inframe_deletion Exon 1 of 1 6 NM_198722.3 ENSP00000323096.7 Q86WK7
RNF123ENST00000327697.11 linkc.3500+1740_3500+1748delGGCAGCGGC intron_variant Intron 35 of 38 1 NM_022064.5 ENSP00000328287.6 Q5XPI4-1

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152156
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00600
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00100
AC:
247
AN:
245970
Hom.:
2
AF XY:
0.00133
AC XY:
178
AN XY:
133776
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.00779
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000365
Gnomad OTH exome
AF:
0.000495
GnomAD4 exome
AF:
0.000530
AC:
774
AN:
1460062
Hom.:
6
AF XY:
0.000757
AC XY:
550
AN XY:
726318
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00828
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.000322
AC XY:
24
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00601
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000131
Hom.:
0
Bravo
AF:
0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs543098573; hg19: chr3-49755642; API