rs143982322

Variant names:

• chr1-62805225-C-A
• rs143982322
• NM_032852.4:c.130C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-62805225-C-A
• chr1-62805225-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032852.4(ATG4C):​c.130C>A​(p.Leu44Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000804 in 1,504,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ATG4C NM_032852.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78
• Publications: 1 publications found

Genes affected

ATG4C (HGNC:16040): (autophagy related 4C 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 the same protein, have been characterized. [provided by RefSeq, Jul 2008]

ENSG00000306496 (HGNC:58931):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12968716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032852.4. 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
	ATG4C	NM_032852.4	MANE Select	c.130C>A	p.Leu44Ile	missense	Exon 3 of 11	NP_116241.2
	ATG4C	NM_178221.3		c.130C>A	p.Leu44Ile	missense	Exon 3 of 11	NP_835739.1	A0A384MTY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4C	ENST00000317868.9	TSL:1 MANE Select	c.130C>A	p.Leu44Ile	missense	Exon 3 of 11	ENSP00000322159.4	Q96DT6
	ATG4C	ENST00000371120.7	TSL:1	c.130C>A	p.Leu44Ile	missense	Exon 3 of 11	ENSP00000360161.3	Q96DT6
	ATG4C	ENST00000852843.1		c.130C>A	p.Leu44Ile	missense	Exon 3 of 12	ENSP00000522902.1

Frequencies

GnomAD3 genomes AF: 0.000482 AC: 72 AN: 149458 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00175

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: 0.00

Gnomad OTH AF: 0.000487

GnomAD2 exomes AF: 0.0000630 AC: 11 AN: 174512 AF XY: 0.0000310

Gnomad AFR exome AF: 0.000842

Gnomad AMR exome AF: 0.0000625

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000362 AC: 49 AN: 1355044 Hom.: 0 Cov.: 34 AF XY: 0.0000298 AC XY: 20 AN XY: 671690

African (AFR) AF: 0.00151 AC: 41 AN: 27208

American (AMR) AF: 0.000118 AC: 3 AN: 25430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23082

East Asian (EAS) AF: 0.00 AC: 0 AN: 32976

South Asian (SAS) AF: 0.00 AC: 0 AN: 66344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 9.36e-7 AC: 1 AN: 1068054

Other (OTH) AF: 0.0000720 AC: 4 AN: 55594

GnomAD4 genome AF: 0.000481 AC: 72 AN: 149544 Hom.: 0 Cov.: 32 AF XY: 0.000494 AC XY: 36 AN XY: 72864

African (AFR) AF: 0.00175 AC: 71 AN: 40644

American (AMR) AF: 0.00 AC: 0 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67606

Other (OTH) AF: 0.000483 AC: 1 AN: 2070

Alfa AF: 0.000250 Hom.: 0

Bravo AF: 0.000446

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000989 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.59
MVP		0.58
MPC		0.093
ClinPred		0.14	T
GERP RS		4.5
Varity_R		0.34
gMVP		0.67
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs143982322; hg19: chr1-63270896;