rs773384073

Variant names:

• chr16-81315130-C-A
• NM_022041.4:c.17C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-81315130-C-A
• chr16-81315130-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022041.4(GAN):​c.17C>A​(p.Ala6Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,369,480 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. Synonymous variant affecting the same amino acid position (i.e. AV6A?) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: GAN NM_022041.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23933503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAN	NM_022041.4	c.17C>A	p.Ala6Asp	missense_variant	Exon 1 of 11	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1	c.-508C>A		5_prime_UTR_variant	Exon 1 of 10		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2	c.17C>A	p.Ala6Asp	missense_variant	Exon 1 of 11		NM_022041.4	ENSP00000497351.1
GAN	ENST00000648349.2	n.17C>A		non_coding_transcript_exon_variant	Exon 1 of 10			ENSP00000498114.1
GAN	ENST00000650388.1	n.17C>A		non_coding_transcript_exon_variant	Exon 1 of 9			ENSP00000498081.1
GAN	ENST00000674788.1	n.142C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369480 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 676770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000299

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	.;T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.030	N;N
PrimateAI	Pathogenic	0.96	D
Sift4G	Benign	0.092	T;.
Polyphen		0.0050	B;B
Vest4		0.52
MutPred		0.22		Loss of glycosylation at S5 (P = 0.0451);Loss of glycosylation at S5 (P = 0.0451);
MVP		0.84
MPC		0.18
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.55
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-81348735;