rs768562044

Variant names:

• chr16-81363855-A-G
• NM_022041.4:c.1148A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-81363855-A-G
• chr16-81363855-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022041.4(GAN):​c.1148A>G​(p.Asp383Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,508 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GAN NM_022041.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34480205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAN	NM_022041.4	c.1148A>G	p.Asp383Gly	missense_variant	Exon 7 of 11	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1	c.509A>G	p.Asp170Gly	missense_variant	Exon 6 of 10		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2	c.1148A>G	p.Asp383Gly	missense_variant	Exon 7 of 11		NM_022041.4	ENSP00000497351.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459508 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

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	0.25
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D;D
Eigen	Benign	0.011
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.13	T;.
Polyphen		0.0040	B;B
Vest4		0.60
MutPred		0.58		Gain of methylation at K386 (P = 0.0659);Gain of methylation at K386 (P = 0.0659);
MVP		0.64
MPC		0.16
ClinPred		0.91	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.56
gMVP		0.70

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: chr16-81397460;