GeneBe

rs201884522

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_022041.4(GAN):​c.564C>G​(p.Asn188Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N188N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

GAN
NM_022041.4 missense

Scores

2
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.210

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Trascript score misZ: -2.0288 (below the threshold of 3.09). GenCC associations: The gene is linked to giant axonal neuropathy 1.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022041.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GAN
NM_022041.4
MANE Select
c.564C>Gp.Asn188Lys
missense
Exon 3 of 11NP_071324.1A0A0S2Z4W2
GAN
NM_001377486.1
c.-76C>G
5_prime_UTR
Exon 2 of 10NP_001364415.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GAN
ENST00000648994.2
MANE Select
c.564C>Gp.Asn188Lys
missense
Exon 3 of 11ENSP00000497351.1Q9H2C0
GAN
ENST00000718305.1
c.564C>Gp.Asn188Lys
missense
Exon 3 of 11ENSP00000520738.1Q9H2C0
GAN
ENST00000880995.1
c.283-2099C>G
intron
N/AENSP00000551054.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Giant axonal neuropathy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Uncertain
0.76
D
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.1
M
PhyloP100
-0.21
PrimateAI
Pathogenic
0.80
T
Sift4G
Benign
0.15
T
Polyphen
0.28
B
Vest4
0.89
MutPred
0.81
Gain of ubiquitination at N188 (P = 0.023)
MVP
0.33
MPC
0.16
ClinPred
0.36
T
GERP RS
-9.5
Varity_R
0.63
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.40
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.40
Position offset: 0

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

Publications

Other links and lift over

dbSNP: rs201884522; hg19: chr16-81388291; API