rs886038666

Variant names:

• chr16-81315292-G-A
• rs886038666
• NM_022041.4:c.167+12G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-81315292-G-A
• chr16-81315292-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022041.4(GAN):​c.167+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,368,472 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: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: GAN NM_022041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAN	NM_022041.4	c.167+12G>A		intron_variant	Intron 1 of 10	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1	c.-358+12G>A		intron_variant	Intron 1 of 9		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2	c.167+12G>A		intron_variant	Intron 1 of 10		NM_022041.4	ENSP00000497351.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000365 AC: 5 AN: 1368472 Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 2 AN XY: 678722

African (AFR) AF: 0.00 AC: 0 AN: 28154

American (AMR) AF: 0.00 AC: 0 AN: 33940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23460

East Asian (EAS) AF: 0.00 AC: 0 AN: 31162

South Asian (SAS) AF: 0.00 AC: 0 AN: 75906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 0.00000469 AC: 5 AN: 1065494

Other (OTH) AF: 0.00 AC: 0 AN: 55926

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		2.6
PromoterAI		0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs886038666; hg19: chr16-81348897;