GeneBe

NM_022041.4:c.601C>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B.

Score: 1 - Uncertain Significance
1
-12 -7 -6 -1 0 5 6 9 10 12
PM2BP4

The NM_022041.4(GAN):​c.601C>A​(p.Arg201Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000069 in 1,449,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GAN
NM_022041.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70

Publications

0 publications found
Variant links:
Genes affected
GAN (HGNC:4137): (gigaxonin) This gene encodes a member of the cytoskeletal BTB/kelch (Broad-Complex, Tramtrack and Bric a brac) repeat family. The encoded protein plays a role in neurofilament architecture and is involved in mediating the ubiquitination and degradation of some proteins. Defects in this gene are a cause of giant axonal neuropathy (GAN). [provided by RefSeq, Oct 2008]
GAN Gene-Disease associations (from GenCC):
  • giant axonal neuropathy 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.18).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GANNM_022041.4 linkc.601C>A p.Arg201Arg synonymous_variant Exon 3 of 11 ENST00000648994.2 NP_071324.1 Q9H2C0A0A0S2Z4W2B3KTC3
GANNM_001377486.1 linkc.-39C>A 5_prime_UTR_variant Exon 2 of 10 NP_001364415.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GANENST00000648994.2 linkc.601C>A p.Arg201Arg synonymous_variant Exon 3 of 11 NM_022041.4 ENSP00000497351.1 Q9H2C0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449838
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
722158
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33228
American (AMR)
AF:
0.00
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26052
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39636
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
85940
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1101074
Other (OTH)
AF:
0.00
AC:
0
AN:
60036
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.18
CADD
Benign
13
DANN
Benign
0.76
PhyloP100
3.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs119485090; hg19: chr16-81388328; API