rs346081

Variant names:

• chr3-11287399-A-G
• rs346081
• NM_001349232.2:c.-11+4961A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-11287399-A-G
• chr3-11287399-A-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.-11+4961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,178 control chromosomes in the GnomAD database, including 56,957 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 (56957 hom., cov: 31)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 6 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=-0.98).
• 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.-11+4961A>G		intron_variant	Intron 3 of 20	ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.-11+4961A>G		intron_variant	Intron 3 of 20		NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131268 AN: 152060 Hom.: 56898 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.863 AC: 131388 AN: 152178 Hom.: 56957 Cov.: 31 AF XY: 0.867 AC XY: 64518 AN XY: 74386

African (AFR) AF: 0.911 AC: 37836 AN: 41528

American (AMR) AF: 0.875 AC: 13381 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2515 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5164 AN: 5170

South Asian (SAS) AF: 0.925 AC: 4458 AN: 4820

European-Finnish (FIN) AF: 0.888 AC: 9395 AN: 10584

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.822 AC: 55932 AN: 68010

Other (OTH) AF: 0.864 AC: 1817 AN: 2104

Alfa AF: 0.852 Hom.: 7989

Bravo AF: 0.866

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.044
DANN	Benign	0.64
PhyloP100		-1.3
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: rs346081; hg19: chr3-11329085;