6-106286165-C-T

Variant names:

• chr6-106286165-C-T
• rs633724
• NM_004849.4:c.316-6342G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004849.4(ATG5):​c.316-6342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,968 control chromosomes in the GnomAD database, including 13,678 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13678 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 16 publications found

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]

ATG5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 25

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.316-6342G>A		intron_variant	Intron 4 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.316-6342G>A		intron_variant	Intron 4 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63648 AN: 151850 Hom.: 13642 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63746 AN: 151968 Hom.: 13678 Cov.: 32 AF XY: 0.424 AC XY: 31473 AN XY: 74282

African (AFR) AF: 0.484 AC: 20035 AN: 41430

American (AMR) AF: 0.519 AC: 7936 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2335 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4816

European-Finnish (FIN) AF: 0.390 AC: 4108 AN: 10540

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25041 AN: 67966

Other (OTH) AF: 0.407 AC: 857 AN: 2104

Alfa AF: 0.387 Hom.: 49554

Bravo AF: 0.436

Asia WGS AF: 0.423 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs633724; hg19: chr6-106734040; COSMIC: COSV58350019; COSMIC: COSV58350019;