3-11508122-C-T

Variant names:

• chr3-11508122-C-T
• rs2454513
• NM_001349232.2:c.2080-46689C>T

Variant summary

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

The NM_001349232.2(ATG7):​c.2080-46689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,044 control chromosomes in the GnomAD database, including 57,136 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 0.86 (57136 hom., cov: 30)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 7 publications found

Genes affected

ATG7 (HGNC:16935): (autophagy related 7) This gene encodes an E1-like activating enzyme that is essential for autophagy and cytoplasmic to vacuole transport. The encoded protein is also thought to modulate p53-dependent cell cycle pathways during prolonged metabolic stress. It has been associated with multiple functions, including axon membrane trafficking, axonal homeostasis, mitophagy, adipose differentiation, and hematopoietic stem cell maintenance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ATG7 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 31

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG7	NM_001349232.2	c.2080-46689C>T		intron_variant	Intron 20 of 20	ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.2080-46689C>T		intron_variant	Intron 20 of 20		NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131280 AN: 151928 Hom.: 57073 Cov.: 30

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.864 AC: 131403 AN: 152044 Hom.: 57136 Cov.: 30 AF XY: 0.869 AC XY: 64569 AN XY: 74324

African (AFR) AF: 0.945 AC: 39189 AN: 41490

American (AMR) AF: 0.864 AC: 13206 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2465 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5160 AN: 5166

South Asian (SAS) AF: 0.910 AC: 4385 AN: 4818

European-Finnish (FIN) AF: 0.885 AC: 9328 AN: 10542

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54971 AN: 67962

Other (OTH) AF: 0.862 AC: 1820 AN: 2112

Alfa AF: 0.850 Hom.: 18437

Bravo AF: 0.867

Asia WGS AF: 0.948 AC: 3296 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	1.1
DANN	Benign	0.37
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2454513; hg19: chr3-11549596;