chr11-63646550-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_015459.5(ATL3):​c.575A>G​(p.Tyr192Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y192Y) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ATL3
NM_015459.5 missense

Scores

14
4
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.97
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.969
PP5
Variant 11-63646550-T-C is Pathogenic according to our data. Variant chr11-63646550-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 97070.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATL3NM_015459.5 linkuse as main transcriptc.575A>G p.Tyr192Cys missense_variant 6/13 ENST00000398868.8
ATL3NM_001290048.2 linkuse as main transcriptc.521A>G p.Tyr174Cys missense_variant 6/13
ATL3XM_047426725.1 linkuse as main transcriptc.731A>G p.Tyr244Cys missense_variant 7/14
ATL3XM_006718493.2 linkuse as main transcriptc.562-2289A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATL3ENST00000398868.8 linkuse as main transcriptc.575A>G p.Tyr192Cys missense_variant 6/131 NM_015459.5
ENST00000540307.1 linkuse as main transcriptn.60-4010T>C intron_variant, non_coding_transcript_variant 3
ATL3ENST00000538786.1 linkuse as main transcriptc.521A>G p.Tyr174Cys missense_variant 6/132 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 01, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.54
D
MetaRNN
Pathogenic
0.97
D;D
MetaSVM
Uncertain
0.17
D
MutationAssessor
Pathogenic
3.9
H;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-8.5
D;D
REVEL
Pathogenic
0.93
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.95
MVP
0.90
MPC
1.1
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.94
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs587777108; hg19: chr11-63414022; API