Genetic Variant ATL3:p.Asp214Asp (chr11-63644238-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_015459.5(ATL3):c.642T>C(p.Asp214Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,607,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ATL3
NM_015459.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.715

Publications

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

ATL3 links:

ENSG00000256789 (HGNC:58146):

ENSG00000256789 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-63644238-A-G is Benign according to our data. Variant chr11-63644238-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.715 with no splicing effect.

BS2

High AC in GnomAd4 at 42 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
ATL3	NM_015459.5	MANE Select	c.642T>C	p.Asp214Asp	synonymous	Exon 7 of 13	NP_056274.3
ATL3	NM_001440716.1		c.591T>C	p.Asp197Asp	synonymous	Exon 6 of 12	NP_001427645.1
ATL3	NM_001290048.2		c.588T>C	p.Asp196Asp	synonymous	Exon 7 of 13	NP_001276977.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATL3	ENST00000398868.8	TSL:1 MANE Select	c.642T>C	p.Asp214Asp	synonymous	Exon 7 of 13	ENSP00000381844.3
ATL3	ENST00000538786.1	TSL:2	c.588T>C	p.Asp196Asp	synonymous	Exon 7 of 13	ENSP00000437593.1
ENSG00000256789	ENST00000540307.2	TSL:3	n.366-6322A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00596

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000397

AC:

AN:

244580

AF XY:

0.000354

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00452

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000671

GnomAD4 exome

AF:

0.000113

AC:

164

AN:

1455690

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

724220

show subpopulations

African (AFR)

AF:

0.0000603

AC:

AN:

33176

American (AMR)

AF:

0.0000229

AC:

AN:

43718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00233

AC:

AN:

39556

South Asian (SAS)

AF:

0.000412

AC:

AN:

84986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108906

Other (OTH)

AF:

0.000532

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.000276

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00598

AC:

AN:

5188

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.0000854

Hom.:

Bravo

AF:

0.000227

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F

Benign:1

Sep 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Jul 11, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.1

(source)

DANN

Benign

0.68

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over