3-11274457-C-T

Variant names:

• chr3-11274457-C-T
• rs2594989
• NM_001349232.2:c.-366+2027C>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.-366+2027C>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 152,130 control chromosomes in the GnomAD database, including 57,073 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 (57073 hom., cov: 31)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 5 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=-0.9).
• 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.-366+2027C>T		intron_variant	Intron 1 of 20	ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.-366+2027C>T		intron_variant	Intron 1 of 20		NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131367 AN: 152012 Hom.: 57016 Cov.: 31

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.791

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: 0.864 AC: 131482 AN: 152130 Hom.: 57073 Cov.: 31 AF XY: 0.868 AC XY: 64572 AN XY: 74350

African (AFR) AF: 0.915 AC: 37987 AN: 41528

American (AMR) AF: 0.874 AC: 13353 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2530 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5152 AN: 5158

South Asian (SAS) AF: 0.924 AC: 4448 AN: 4812

European-Finnish (FIN) AF: 0.888 AC: 9396 AN: 10576

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55906 AN: 67994

Other (OTH) AF: 0.864 AC: 1821 AN: 2108

Alfa AF: 0.845 Hom.: 4821

Bravo AF: 0.874

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.37
PhyloP100		0.25
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: rs2594989; hg19: chr3-11316143;