NM_015459.5:c.955C>T

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

7
7
5

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]

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 rank MANE Protein UniProt
ATL3NM_015459.5 linkc.955C>T p.Arg319Trp missense_variant Exon 9 of 13 ENST00000398868.8 NP_056274.3 Q6DD88
ATL3NM_001290048.2 linkc.901C>T p.Arg301Trp missense_variant Exon 9 of 13 NP_001276977.1 Q6DD88F5H6I7B4DXC4
ATL3XM_047426725.1 linkc.1111C>T p.Arg371Trp missense_variant Exon 10 of 14 XP_047282681.1
ATL3XM_006718493.2 linkc.898C>T p.Arg300Trp missense_variant Exon 8 of 12 XP_006718556.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATL3ENST00000398868.8 linkc.955C>T p.Arg319Trp missense_variant Exon 9 of 13 1 NM_015459.5 ENSP00000381844.3 Q6DD88
ATL3ENST00000538786.1 linkc.901C>T p.Arg301Trp missense_variant Exon 9 of 13 2 ENSP00000437593.1 F5H6I7

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249482
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
11
AN:
1461804
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
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.:
30
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000166
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Long QT syndrome Benign:1
-
Medical Research Institute, Tokyo Medical and Dental University
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
0.0055
T
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Benign
0.72
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Benign
-0.34
T
MutationAssessor
Pathogenic
3.4
M;.
PrimateAI
Uncertain
0.76
T
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
D
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.

Other links and lift over

dbSNP: rs776571949; hg19: chr11-63403702; COSMIC: COSV100219637; COSMIC: COSV100219637; API