rs112847445

Positions:

chr11-63631078-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/21 in silico tools predict 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

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.769

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 474835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 381 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATL3	NM_015459.5 linkuse as main transcript	c.1501G>A	p.Gly501Arg	missense_variant	12/13	ENST00000398868.8
ATL3	NM_001290048.2 linkuse as main transcript	c.1447G>A	p.Gly483Arg	missense_variant	12/13
ATL3	XM_047426725.1 linkuse as main transcript	c.1657G>A	p.Gly553Arg	missense_variant	13/14
ATL3	XM_006718493.2 linkuse as main transcript	c.1444G>A	p.Gly482Arg	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATL3	ENST00000398868.8 linkuse as main transcript	c.1501G>A	p.Gly501Arg	missense_variant	12/13	1	NM_015459.5
ATL3	ENST00000538786.1 linkuse as main transcript	c.1447G>A	p.Gly483Arg	missense_variant	12/13	2		P1

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

GnomAD3 exomes

AF:

0.000671

AC:

167

AN:

248926

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

135014

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 SAS exome

AF:

0.000196

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

Gnomad4 AFR exome

AF:

0.00726

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00250

AC:

381

AN:

152222

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00864

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000551

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

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ATL3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.077

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

0.039

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.7

N;N

REVEL

Uncertain

0.43

Sift

Benign

0.42

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.86

P;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over