rs563049431

Variant names:

• chr16-81365024-C-G
• rs563049431
• NM_022041.4:c.1287C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-81365024-C-G
• chr16-81365024-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_022041.4(GAN):​c.1287C>G​(p.Gly429Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G429G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GAN NM_022041.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-81365024-C-G is Benign according to our data. Variant chr16-81365024-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 261480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAN	NM_022041.4	MANE Select	c.1287C>G	p.Gly429Gly	synonymous	Exon 8 of 11	NP_071324.1	A0A0S2Z4W2
	GAN	NM_001377486.1		c.648C>G	p.Gly216Gly	synonymous	Exon 7 of 10	NP_001364415.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAN	ENST00000648994.2	MANE Select	c.1287C>G	p.Gly429Gly	synonymous	Exon 8 of 11	ENSP00000497351.1	Q9H2C0
	GAN	ENST00000718305.1		c.1287C>G	p.Gly429Gly	synonymous	Exon 8 of 11	ENSP00000520738.1	Q9H2C0
	GAN	ENST00000880995.1		c.936C>G	p.Gly312Gly	synonymous	Exon 7 of 10	ENSP00000551054.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Giant axonal neuropathy 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.12
DANN	Benign	0.52
PhyloP100		-1.0

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

Other links and lift over

dbSNP: rs563049431; hg19: chr16-81398629;