chr16-81382086-T-C

Variant names:

• chr16-81382086-T-C
• rs16955238
• NM_022041.4:c.*4490T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022041.4(GAN):​c.*4490T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,150 control chromosomes in the GnomAD database, including 430 homozygotes. 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: 𝑓 0.055 (430 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GAN NM_022041.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAN	NM_022041.4	MANE Select	c.*4490T>C		3_prime_UTR	Exon 11 of 11	NP_071324.1
	GAN	NM_001377486.1		c.*4490T>C		3_prime_UTR	Exon 10 of 10	NP_001364415.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAN	ENST00000648994.2	MANE Select	c.*4490T>C		3_prime_UTR	Exon 11 of 11	ENSP00000497351.1
	GAN	ENST00000718305.1		c.*4490T>C		3_prime_UTR	Exon 11 of 11	ENSP00000520738.1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8311 AN: 152032 Hom.: 429 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0440

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0547 AC: 8328 AN: 152150 Hom.: 430 Cov.: 32 AF XY: 0.0535 AC XY: 3981 AN XY: 74398

African (AFR) AF: 0.140 AC: 5817 AN: 41472

American (AMR) AF: 0.0284 AC: 434 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3466

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4816

European-Finnish (FIN) AF: 0.0176 AC: 187 AN: 10602

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1495 AN: 67998

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0502 Hom.: 49

Bravo AF: 0.0572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.86
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs16955238; hg19: chr16-81415691;