rs116074753
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001103146.3(GIGYF2):c.1370A>C(p.Asn457Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,613,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 1 hom. )
Consequence
GIGYF2
NM_001103146.3 missense
NM_001103146.3 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: -0.758
Genes affected
GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.06393552).
BS2
?
High AC in GnomAd at 53 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIGYF2 | NM_001103146.3 | c.1370A>C | p.Asn457Thr | missense_variant | 13/29 | ENST00000373563.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIGYF2 | ENST00000373563.9 | c.1370A>C | p.Asn457Thr | missense_variant | 13/29 | 1 | NM_001103146.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000349 AC: 53AN: 151920Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000394 AC: 99AN: 251254Hom.: 1 AF XY: 0.000390 AC XY: 53AN XY: 135772
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GnomAD4 exome AF: 0.000478 AC: 698AN: 1461608Hom.: 1 Cov.: 31 AF XY: 0.000458 AC XY: 333AN XY: 727150
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GnomAD4 genome ? AF: 0.000349 AC: 53AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74320
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ESP6500AA
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ESP6500EA
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12
ExAC
?
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47
Asia WGS
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3478
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ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Parkinson disease 11, autosomal dominant, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Aug 01, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;.;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
A;A;A;A;A;A;A
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
0.0
.;B;.;B;.;.;.;.
Vest4
MVP
MPC
0.33
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at