Variant chr11-63636230-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2

The NM_015459.5(ATL3):c.955C>T(p.Arg319Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ATL3
NM_015459.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.64

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 Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.879

BP6

Variant 11-63636230-G-A is Benign according to our data. Variant chr11-63636230-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 207833.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATL3	NM_015459.5 linkuse as main transcript	c.955C>T	p.Arg319Trp	missense_variant	9/13	ENST00000398868.8	NP_056274.3
ATL3	NM_001290048.2 linkuse as main transcript	c.901C>T	p.Arg301Trp	missense_variant	9/13		NP_001276977.1
ATL3	XM_047426725.1 linkuse as main transcript	c.1111C>T	p.Arg371Trp	missense_variant	10/14		XP_047282681.1
ATL3	XM_006718493.2 linkuse as main transcript	c.898C>T	p.Arg300Trp	missense_variant	8/12		XP_006718556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8 linkuse as main transcript	c.955C>T	p.Arg319Trp	missense_variant	9/13	1	NM_015459.5	ENSP00000381844
ATL3	ENST00000538786.1 linkuse as main transcript	c.901C>T	p.Arg301Trp	missense_variant	9/13	2		ENSP00000437593	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249482

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

0.0055

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.72

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.87

MVP

0.74

MPC

1.0

ClinPred

1.0

GERP RS

3.5

Varity_R

0.82

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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