rs200918566

Positions:

chr11-63658793-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.373G>A(p.Val125Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00181 in 1,610,208 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

ATL3
NM_015459.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.11

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:

ENSG00000256789 (HGNC:):

ENSG00000256789 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=0.04737425).

BP6

Variant 11-63658793-C-T is Benign according to our data. Variant chr11-63658793-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATL3	NM_015459.5 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	3/13	ENST00000398868.8	NP_056274.3	Q6DD88
ATL3	NM_001290048.2 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	3/13		NP_001276977.1	Q6DD88F5H6I7B4DXC4
ATL3	XM_047426725.1 linkuse as main transcript	c.529G>A	p.Val177Ile	missense_variant	4/14		XP_047282681.1
ATL3	XM_006718493.2 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	3/12		XP_006718556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATL3	ENST00000398868.8 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	3/13	1	NM_015459.5	ENSP00000381844.3	Q6DD88
ATL3	ENST00000538786.1 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	3/13	2		ENSP00000437593.1	F5H6I7
ENSG00000256789	ENST00000540307.1 linkuse as main transcript	n.254C>T		non_coding_transcript_exon_variant	3/3	3
ATL3	ENST00000540699.1 linkuse as main transcript	c.*21G>A		downstream_gene_variant		3		ENSP00000441842.1	F5GWF8

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000737

AC:

181

AN:

245728

Hom.:

AF XY:

0.000713

AC XY:

AN XY:

133156

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00135

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.00188

AC:

2743

AN:

1457908

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1297

AN XY:

724962

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.000137

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00219

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152300

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00147

AC:

ExAC

AF:

0.000786

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2021

This alteration is classified as 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

ATL3: BP4, BS1, BS2 -

ATL3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2022

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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

0.065

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0095

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.16

Sift

Benign

0.28

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.010

B;.

Vest4

0.25

MVP

0.67

MPC

0.30

ClinPred

0.025

GERP RS

4.9

Varity_R

0.29

gMVP

0.26

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

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