16-81365030-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022041.4(GAN):c.1293C>T(p.Tyr431Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,612,604 control chromosomes in the GnomAD database, including 43,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3607 hom., cov: 31)

Exomes 𝑓: 0.23 ( 39650 hom. )

Consequence

GAN
NM_022041.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.193

Publications

19 publications found

Variant links:

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

GAN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-81365030-C-T is Benign according to our data. Variant chr16-81365030-C-T is described in ClinVar as Benign. ClinVar VariationId is 129131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.193 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAN	NM_022041.4 link	c.1293C>T	p.Tyr431Tyr	synonymous_variant	Exon 8 of 11	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1 link	c.654C>T	p.Tyr218Tyr	synonymous_variant	Exon 7 of 10		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2 link	c.1293C>T	p.Tyr431Tyr	synonymous_variant	Exon 8 of 11		NM_022041.4	ENSP00000497351.1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32041

AN:

151902

Hom.:

3606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.0350

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.222

GnomAD2 exomes

AF:

0.194

AC:

48729

AN:

251396

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.0287

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.227

AC:

331134

AN:

1460584

Hom.:

39650

Cov.:

AF XY:

0.226

AC XY:

163925

AN XY:

726616

show subpopulations

African (AFR)

AF:

0.185

AC:

6181

AN:

33452

American (AMR)

AF:

0.128

AC:

5746

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

5276

AN:

26134

East Asian (EAS)

AF:

0.0417

AC:

1655

AN:

39696

South Asian (SAS)

AF:

0.149

AC:

12846

AN:

86234

European-Finnish (FIN)

AF:

0.215

AC:

11507

AN:

53410

Middle Eastern (MID)

AF:

0.194

AC:

1115

AN:

5756

European-Non Finnish (NFE)

AF:

0.247

AC:

274066

AN:

1110820

Other (OTH)

AF:

0.211

AC:

12742

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

12804

25608

38411

51215

64019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9050

18100

27150

36200

45250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.211

AC:

32058

AN:

152020

Hom.:

3607

Cov.:

AF XY:

0.206

AC XY:

15293

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.189

AC:

7817

AN:

41464

American (AMR)

AF:

0.171

AC:

2618

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

706

AN:

3470

East Asian (EAS)

AF:

0.0349

AC:

180

AN:

5164

South Asian (SAS)

AF:

0.147

AC:

708

AN:

4818

European-Finnish (FIN)

AF:

0.212

AC:

2241

AN:

10550

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17095

AN:

67964

Other (OTH)

AF:

0.221

AC:

465

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1278

2557

3835

5114

6392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.235

Hom.:

7817

Bravo

AF:

0.203

Asia WGS

AF:

0.111

AC:

389

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.258

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Giant axonal neuropathy 1

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Oct 09, 2014

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

This SCV is no longer cited in the GeneReview (NBK1136). -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.98

(source)

DANN

Benign

0.25

PhyloP100

0.19

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over