6-106189700-C-T

Variant names:

• chr6-106189700-C-T
• rs6920944
• NM_004849.4:c.692-3024G>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.692-3024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 150,702 control chromosomes in the GnomAD database, including 1,024 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 0.11 (1024 hom., cov: 31)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 7 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

ENSG00000303838 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 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.692-3024G>A		intron	N/A	NP_004840.1	A9UGY9
	ATG5	NM_001286106.2		c.692-3024G>A		intron	N/A	NP_001273035.1	Q9H1Y0-1
	ATG5	NM_001286108.2		c.*46-3024G>A		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.692-3024G>A		intron	N/A	ENSP00000358072.3	Q9H1Y0-1
	ATG5	ENST00000343245.7	TSL:1	c.692-3024G>A		intron	N/A	ENSP00000343313.3	Q9H1Y0-1
	ATG5	ENST00000635758.2	TSL:1	c.458-3024G>A		intron	N/A	ENSP00000490493.1	Q9H1Y0-2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16881 AN: 150614 Hom.: 1023 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0243

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.110

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.112 AC: 16912 AN: 150702 Hom.: 1024 Cov.: 31 AF XY: 0.115 AC XY: 8435 AN XY: 73554

African (AFR) AF: 0.155 AC: 6375 AN: 41132

American (AMR) AF: 0.114 AC: 1720 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.0487 AC: 251 AN: 5154

South Asian (SAS) AF: 0.157 AC: 752 AN: 4796

European-Finnish (FIN) AF: 0.0893 AC: 894 AN: 10016

Middle Eastern (MID) AF: 0.119 AC: 34 AN: 286

European-Non Finnish (NFE) AF: 0.0943 AC: 6383 AN: 67720

Other (OTH) AF: 0.0981 AC: 206 AN: 2100

Alfa AF: 0.105 Hom.: 469

Bravo AF: 0.114

Asia WGS AF: 0.142 AC: 495 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.97
DANN	Benign	0.59
PhyloP100		0.23
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: rs6920944; hg19: chr6-106637575; COSMIC: COSV58346696;