chr16-81382086-T-C

Position:

• chr16-81382086-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAN	NM_022041.4	c.*4490T>C		3_prime_UTR_variant	11/11	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1	c.*4490T>C		3_prime_UTR_variant	10/10		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2	c.*4490T>C		3_prime_UTR_variant	11/11		NM_022041.4	ENSP00000497351	P1

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0284

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0476 Hom.: 42

Bravo AF: 0.0572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs16955238; hg19: chr16-81415691;