3-11358775-C-T

Variant names:

• chr3-11358775-C-T
• rs2606736
• NM_001349232.2:c.1479+163C>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.1479+163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,060 control chromosomes in the GnomAD database, including 22,950 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 0.54 (22950 hom., cov: 32)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 49 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG7	NM_001349232.2	c.1479+163C>T		intron_variant	Intron 15 of 20	ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.1479+163C>T		intron_variant	Intron 15 of 20		NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82288 AN: 151942 Hom.: 22945 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.541 AC: 82320 AN: 152060 Hom.: 22950 Cov.: 32 AF XY: 0.537 AC XY: 39933 AN XY: 74332

African (AFR) AF: 0.414 AC: 17171 AN: 41464

American (AMR) AF: 0.471 AC: 7187 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1757 AN: 3472

East Asian (EAS) AF: 0.675 AC: 3481 AN: 5158

South Asian (SAS) AF: 0.533 AC: 2568 AN: 4818

European-Finnish (FIN) AF: 0.567 AC: 5996 AN: 10584

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42350 AN: 67984

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.598 Hom.: 82610

Bravo AF: 0.531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		-0.13
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: rs2606736; hg19: chr3-11400249;