rs9372120

Variant names:

• chr6-106219660-T-G
• rs9372120
• NM_004849.4:c.574-17571A>C

Variant summary

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

The NM_004849.4(ATG5):​c.574-17571A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,072 control chromosomes in the GnomAD database, including 2,178 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 0.16 (2178 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.574-17571A>C		intron_variant	Intron 6 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.574-17571A>C		intron_variant	Intron 6 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23629 AN: 151954 Hom.: 2180 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.155 AC: 23624 AN: 152072 Hom.: 2178 Cov.: 32 AF XY: 0.155 AC XY: 11541 AN XY: 74332

African (AFR) AF: 0.0727 AC: 3019 AN: 41520

American (AMR) AF: 0.152 AC: 2317 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.0475 AC: 246 AN: 5184

South Asian (SAS) AF: 0.162 AC: 779 AN: 4814

European-Finnish (FIN) AF: 0.220 AC: 2332 AN: 10576

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

European-Non Finnish (NFE) AF: 0.203 AC: 13799 AN: 67908

Other (OTH) AF: 0.147 AC: 310 AN: 2112

Alfa AF: 0.177 Hom.: 4768

Bravo AF: 0.144

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.18
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: rs9372120; hg19: chr6-106667535;