11-63631078-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015459.5(ATL3):c.1501G>A(p.Gly501Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,613,802 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

ATL3
NM_015459.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.769

Publications

4 publications found

Variant links:

Genes affected

ATL3 (HGNC:24526): (atlastin GTPase 3) This gene encodes a member of a family of dynamin-like, integral membrane GTPases. The encoded protein is required for the proper formation of the network of interconnected tubules of the endoplasmic reticulum. Mutations in this gene may be associated with hereditary sensory neuropathy type IF. Alternatively spliced transcript variants that encode distinct isoforms have been described. [provided by RefSeq, Feb 2014]

ATL3 Gene-Disease associations (from GenCC):

neuropathy, hereditary sensory, type 1F
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
hereditary sensory and autonomic neuropathy type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ATL3 links:

LNCROPM (HGNC:58146):

LNCROPM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010328501).

BP6

Variant 11-63631078-C-T is Benign according to our data. Variant chr11-63631078-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 381 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015459.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATL3	NM_015459.5	MANE Select	c.1501G>A	p.Gly501Arg	missense	Exon 12 of 13	NP_056274.3
ATL3	NM_001440716.1		c.1450G>A	p.Gly484Arg	missense	Exon 11 of 12	NP_001427645.1
ATL3	NM_001290048.2		c.1447G>A	p.Gly483Arg	missense	Exon 12 of 13	NP_001276977.1	F5H6I7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATL3	ENST00000398868.8	TSL:1 MANE Select	c.1501G>A	p.Gly501Arg	missense	Exon 12 of 13	ENSP00000381844.3	Q6DD88
ATL3	ENST00000955365.1		c.1498G>A	p.Gly500Arg	missense	Exon 12 of 13	ENSP00000625424.1
ATL3	ENST00000538786.1	TSL:2	c.1447G>A	p.Gly483Arg	missense	Exon 12 of 13	ENSP00000437593.1	F5H6I7

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

380

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000671

AC:

167

AN:

248926

AF XY:

0.000467

show subpopulations

Gnomad AFR exome

AF:

0.00872

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000243

AC:

355

AN:

1461580

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.00726

AC:

243

AN:

33476

American (AMR)

AF:

0.000470

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.000186

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1111820

Other (OTH)

AF:

0.000563

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00250

AC:

381

AN:

152222

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00864

AC:

359

AN:

41542

American (AMR)

AF:

0.000850

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68010

Other (OTH)

AF:

0.00190

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00108

Hom.:

Bravo

AF:

0.00258

ESP6500AA

AF:

0.00740

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000843

AC:

102

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

ATL3-related disorder (1)

Inborn genetic diseases (1)

Neuropathy, hereditary sensory, type 1F (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

Eigen

Benign

-0.077

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.039

MutationAssessor

Benign

1.9

PhyloP100

0.77

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.43

Sift

Benign

0.42

Sift4G

Benign

0.53

Polyphen

0.86

Vest4

0.49

MutPred

0.38

Gain of methylation at G501 (P = 0.0175)

MVP

0.98

MPC

1.0

ClinPred

0.012

GERP RS

4.4

Varity_R

0.099

gMVP

0.75

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over