rs1769972

Variant names:

• chr6-106227944-T-C
• rs1769972
• NM_004849.4:c.573+20206A>G

Variant summary

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

The NM_004849.4(ATG5):​c.573+20206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 152,150 control chromosomes in the GnomAD database, including 591 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 0.086 (591 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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 (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	NM_004849.4	MANE Select	c.573+20206A>G		intron	N/A	NP_004840.1	A9UGY9
	ATG5	NM_001286106.2		c.573+20206A>G		intron	N/A	NP_001273035.1	Q9H1Y0-1
	ATG5	NM_001286108.2		c.569+20206A>G		intron	N/A	NP_001273037.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000369076.8	TSL:1 MANE Select	c.573+20206A>G		intron	N/A	ENSP00000358072.3	Q9H1Y0-1
	ATG5	ENST00000343245.7	TSL:1	c.573+20206A>G		intron	N/A	ENSP00000343313.3	Q9H1Y0-1
	ATG5	ENST00000635758.2	TSL:1	c.339+20206A>G		intron	N/A	ENSP00000490493.1	Q9H1Y0-2

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13017 AN: 152032 Hom.: 592 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0857 AC: 13032 AN: 152150 Hom.: 591 Cov.: 32 AF XY: 0.0879 AC XY: 6537 AN XY: 74396

African (AFR) AF: 0.0991 AC: 4113 AN: 41496

American (AMR) AF: 0.0970 AC: 1484 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.0463 AC: 240 AN: 5178

South Asian (SAS) AF: 0.128 AC: 617 AN: 4822

European-Finnish (FIN) AF: 0.0869 AC: 920 AN: 10586

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5243 AN: 67986

Other (OTH) AF: 0.0749 AC: 158 AN: 2110

Alfa AF: 0.0829 Hom.: 310

Bravo AF: 0.0859

Asia WGS AF: 0.117 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.57
PhyloP100		-0.42
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: rs1769972; hg19: chr6-106675819;