6-106289275-A-G

Variant names:

• chr6-106289275-A-G
• rs12529626
• NM_004849.4:c.315+3753T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004849.4(ATG5):​c.315+3753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 152,256 control chromosomes in the GnomAD database, including 478 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 0.063 (478 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.315+3753T>C		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.315+3753T>C		intron_variant	Intron 4 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9605 AN: 152138 Hom.: 478 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0631 AC: 9603 AN: 152256 Hom.: 478 Cov.: 32 AF XY: 0.0626 AC XY: 4658 AN XY: 74428

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0784 Hom.: 720

Bravo AF: 0.0557

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12529626; hg19: chr6-106737150;