rs1009961799

Variant names:

• chr2-241654581-A-C
• rs1009961799
• NM_013325.5:c.319A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-241654581-A-C
• chr2-241654581-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013325.5(ATG4B):​c.319A>C​(p.Ser107Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATG4B NM_013325.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20783603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4B	NM_013325.5	c.319A>C	p.Ser107Arg	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.319A>C	p.Ser107Arg	missense_variant	Exon 5 of 13	1	NM_013325.5	ENSP00000384259.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;.;T;T;.;T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.027
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;T;T;.;T;.;.
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N;.;N;.;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N
REVEL	Benign	0.096
Sift	Benign	0.39	T;T;T;T;T;T;T;T
Sift4G	Benign	0.48	T;T;T;T;T;T;T;T
Polyphen		0.0050, 0.0030	.;B;B;.;.;.;.;.
Vest4		0.43
MutPred		0.46		Gain of MoRF binding (P = 0.0172);.;Gain of MoRF binding (P = 0.0172);.;Gain of MoRF binding (P = 0.0172);Gain of MoRF binding (P = 0.0172);.;.;
MVP		0.35
MPC		0.54
ClinPred		0.74	D
GERP RS		5.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.35
gMVP		0.52

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: rs1009961799; hg19: chr2-242593996;