rs10493328

Variant names:

• chr1-62801049-G-A
• rs10493328
• NM_032852.4:c.-68-2670G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032852.4(ATG4C):​c.-68-2670G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,136 control chromosomes in the GnomAD database, including 1,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1691 hom., cov: 32)
• Consequence: ATG4C NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

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.-68-2670G>A		intron	N/A	NP_116241.2
	ATG4C	NM_178221.3		c.-68-2670G>A		intron	N/A	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.-68-2670G>A		intron	N/A	ENSP00000322159.4	Q96DT6
	ATG4C	ENST00000371120.7	TSL:1	c.-68-2670G>A		intron	N/A	ENSP00000360161.3	Q96DT6
	ATG4C	ENST00000852843.1		c.-68-2670G>A		intron	N/A	ENSP00000522902.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22016 AN: 152018 Hom.: 1686 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0987

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.132

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 22032 AN: 152136 Hom.: 1691 Cov.: 32 AF XY: 0.147 AC XY: 10914 AN XY: 74386

African (AFR) AF: 0.129 AC: 5341 AN: 41510

American (AMR) AF: 0.184 AC: 2816 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 342 AN: 3466

East Asian (EAS) AF: 0.0204 AC: 106 AN: 5186

South Asian (SAS) AF: 0.195 AC: 941 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1465 AN: 10584

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10656 AN: 67980

Other (OTH) AF: 0.132 AC: 279 AN: 2114

Alfa AF: 0.157 Hom.: 3279

Bravo AF: 0.148

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.53
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10493328;

hg19: chr1-63266720;

COSMIC: COSV58604605;