chr14-55385881-C-G

Variant names:

• chr14-55385881-C-G
• rs756049156
• NM_014924.5:c.625G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014924.5(ATG14):​c.625G>C​(p.Glu209Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E209K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ATG14 NM_014924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097887605).

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.625G>C	p.Glu209Gln	missense	Exon 5 of 10	NP_055739.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG14	ENST00000247178.6	TSL:1 MANE Select	c.625G>C	p.Glu209Gln	missense	Exon 5 of 10	ENSP00000247178.5	Q6ZNE5-1
	ATG14	ENST00000558189.1	TSL:2	n.608G>C		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459748 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725850

African (AFR) AF: 0.00 AC: 0 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 85956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110748

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.076
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.6
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.033
Sift	Benign	0.47	T
Sift4G	Benign	0.46	T
Polyphen		0.0020	B
Vest4		0.21
MutPred		0.28		Loss of disorder (P = 0.0906)
MVP		0.16
MPC		0.29
ClinPred		0.43	T
GERP RS		4.8
Varity_R		0.11
gMVP		0.24
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs756049156; hg19: chr14-55852599;