rs757216350

Variant names:

• chr16-81377585-C-G
• NM_022041.4:c.1783C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-81377585-C-G
• chr16-81377585-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.1783C>G​(p.His595Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GAN NM_022041.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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=0.14499795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAN	NM_022041.4	c.1783C>G	p.His595Asp	missense_variant	Exon 11 of 11	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1	c.1144C>G	p.His382Asp	missense_variant	Exon 10 of 10		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2	c.1783C>G	p.His595Asp	missense_variant	Exon 11 of 11		NM_022041.4	ENSP00000497351.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.84	T;.
Polyphen		0.0020	B;B
Vest4		0.21
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);
MVP		0.50
MPC		0.17
ClinPred		0.18	T
GERP RS		4.6
Varity_R		0.097
gMVP		0.64

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: chr16-81411190;