3-11331420-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001349232.2(ATG7):c.759C>T(p.Ala253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,600,652 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00092 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (15 hom.)
• Consequence: ATG7 NM_001349232.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-11331420-C-T is Benign according to our data. Variant chr3-11331420-C-T is described in ClinVar as [Benign]. Clinvar id is 732768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00092 (140/152230) while in subpopulation EAS AF= 0.0239 (124/5180). AF 95% confidence interval is 0.0205. There are 1 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG7	NM_001349232.2	c.759C>T	p.Ala253=	synonymous_variant	10/21	ENST00000693202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG7	ENST00000693202.1	c.759C>T	p.Ala253=	synonymous_variant	10/21		NM_001349232.2	P1

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152112 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00195 AC: 490 AN: 251368 Hom.: 7 AF XY: 0.00172 AC XY: 233 AN XY: 135856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.0252

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000751 AC: 1088 AN: 1448422 Hom.: 15 Cov.: 30 AF XY: 0.000708 AC XY: 511 AN XY: 721434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.000537

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.000454

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000346

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.000920 AC: 140 AN: 152230 Hom.: 1 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74426

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0239

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.00113

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	8.4
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs79941725; hg19: chr3-11372894; COSMIC: COSV61612513; COSMIC: COSV61612513;