chr6-106316991-G-A

Variant names:

• chr6-106316991-G-A
• rs573775
• NM_004849.4:c.-58-725C>T

Variant summary

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

The NM_004849.4(ATG5):​c.-58-725C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,828 control chromosomes in the GnomAD database, including 9,327 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 0.34 (9327 hom., cov: 31)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 41 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.-58-725C>T		intron_variant	Intron 1 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.-58-725C>T		intron_variant	Intron 1 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51725 AN: 151710 Hom.: 9305 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.341 AC: 51807 AN: 151828 Hom.: 9327 Cov.: 31 AF XY: 0.344 AC XY: 25524 AN XY: 74188

African (AFR) AF: 0.464 AC: 19192 AN: 41372

American (AMR) AF: 0.295 AC: 4500 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1758 AN: 5162

South Asian (SAS) AF: 0.331 AC: 1598 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3485 AN: 10508

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19519 AN: 67932

Other (OTH) AF: 0.296 AC: 624 AN: 2106

Alfa AF: 0.295 Hom.: 11535

Bravo AF: 0.342

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.40
PhyloP100		-0.39
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: rs573775; hg19: chr6-106764866; COSMIC: COSV58350029; COSMIC: COSV58350029;