Genetic Variant ATG14:c.1172+3090A>G (chr14-55374729-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014924.5(ATG14):c.1172+3090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,054 control chromosomes in the GnomAD database, including 7,067 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 0.30 ( 7067 hom., cov: 32)

Consequence

ATG14
NM_014924.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

9 publications found

Variant links:

Genes affected

ATG14 (HGNC:19962): (autophagy related 14) Enables GTPase binding activity. Involved in several processes, including macroautophagy; regulation of phosphorylation; and response to mitochondrial depolarisation. Acts upstream of or within endosome to lysosome transport. Located in autophagosome and phagophore assembly site membrane. Is extrinsic component of omegasome membrane and extrinsic component of phagophore assembly site membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATG14 links:

FBXO34 (HGNC:20201): (F-box protein 34) Members of the F-box protein family, such as FBXO34, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXO34 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG14	NM_014924.5	MANE Select	c.1172+3090A>G		intron	N/A	NP_055739.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG14	ENST00000247178.6	TSL:1 MANE Select	c.1172+3090A>G		intron	N/A	ENSP00000247178.5	Q6ZNE5-1
	ATG14	ENST00000558189.1	TSL:2	n.1155+3090A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45051

AN:

151936

Hom.:

7062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.267

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

GnomAD4 genome

AF:

0.296

AC:

45076

AN:

152054

Hom.:

7067

Cov.:

AF XY:

0.301

AC XY:

22392

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.217

AC:

8985

AN:

41470

American (AMR)

AF:

0.245

AC:

3738

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

694

AN:

3468

East Asian (EAS)

AF:

0.319

AC:

1650

AN:

5176

South Asian (SAS)

AF:

0.299

AC:

1441

AN:

4814

European-Finnish (FIN)

AF:

0.465

AC:

4911

AN:

10562

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.335

AC:

22788

AN:

67984

Other (OTH)

AF:

0.266

AC:

561

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1631

3262

4894

6525

8156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.307

Hom.:

1361

Bravo

AF:

0.274

Asia WGS

AF:

0.335

AC:

1166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.32

(source)

DANN

Benign

0.26

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over