2-241654600-A-T

Variant names:

• chr2-241654600-A-T
• rs201801584
• NM_013325.5:c.338A>T

Variant summary

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

The NM_013325.5(ATG4B):​c.338A>T​(p.Asn113Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ATG4B NM_013325.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

Genes affected

ATG4B (HGNC:20790): (autophagy related 4B 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 encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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
ATG4B	NM_013325.5	c.338A>T	p.Asn113Ile	missense_variant	Exon 5 of 13	ENST00000404914.8	NP_037457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4B	ENST00000404914.8	c.338A>T	p.Asn113Ile	missense_variant	Exon 5 of 13	1	NM_013325.5	ENSP00000384259.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74290

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	.;.;T;T;.;T;.;T
Eigen	Benign	0.016
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;D;D;D;.;D;.;.
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.50	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.1	M;.;M;.;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.039	D;D;T;D;D;D;D;D
Sift4G	Uncertain	0.054	T;T;D;T;T;T;T;T
Polyphen		0.54, 0.46	.;P;P;.;.;.;.;.
Vest4		0.78
MutPred		0.52		Loss of catalytic residue at N113 (P = 0.0557);.;Loss of catalytic residue at N113 (P = 0.0557);.;Loss of catalytic residue at N113 (P = 0.0557);Loss of catalytic residue at N113 (P = 0.0557);.;.;
MVP		0.61
MPC		0.60
ClinPred		0.98	D
GERP RS		2.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.63
gMVP		0.74

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: rs201801584; hg19: chr2-242594015;