rs762013772

Variant names:

• chr19-10545001-C-G
• NM_032885.6:c.364C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-10545001-C-G
• chr19-10545001-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032885.6(ATG4D):​c.364C>G​(p.Leu122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,188 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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. L122F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATG4D NM_032885.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.782

Genes affected

ATG4D (HGNC:20789): (autophagy related 4D cysteine peptidase) Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene belongs to the autophagy-related protein 4 (Atg4) family of C54 endopeptidases. Members of this family encode proteins that play a role in the biogenesis of autophagosomes, which sequester the cytosol and organelles for degradation by lysosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4D	NM_032885.6	c.364C>G	p.Leu122Val	missense_variant	Exon 3 of 10	ENST00000309469.9	NP_116274.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4D	ENST00000309469.9	c.364C>G	p.Leu122Val	missense_variant	Exon 3 of 10	1	NM_032885.6	ENSP00000311318.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454188 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722932

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T;.
Eigen	Benign	0.010
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.79	P;.
Vest4		0.57
MutPred		0.62		Gain of MoRF binding (P = 0.1204);.;
MVP		0.53
MPC		0.47
ClinPred		0.73	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10655677;