rs1131692265

Positions:

• chr6-106279773-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The ENST00000369076.8(ATG5):​c.366A>T​(p.Glu122Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATG5 ENST00000369076.8 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.54

Genes affected

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879
• PP5: Variant 6-106279773-T-A is Pathogenic according to our data. Variant chr6-106279773-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 430932.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG5	NM_004849.4	c.366A>T	p.Glu122Asp	missense_variant	5/8	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.366A>T	p.Glu122Asp	missense_variant	5/8	1	NM_004849.4	ENSP00000358072	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive 25 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;D;.;D;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;.;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Uncertain	-0.066	T
MutationAssessor	Uncertain	2.9	.;M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	.;D;.;D;.
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0060	.;D;.;D;.
Sift4G	Uncertain	0.0070	.;D;.;D;D
Polyphen		1.0	.;D;D;D;.
Vest4		0.86, 0.85, 0.88
MutPred		0.78		.;Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.76
MPC		1.6
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.96
gMVP		0.58

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

Other links and lift over

dbSNP: rs1131692265; hg19: chr6-106727648;