chr12-52073895-A-C

Position:

• chr12-52073895-A-C

Variant summary

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

The NM_021934.5(ATG101):​c.245A>C​(p.Glu82Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,316,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ATG101 NM_021934.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

Genes affected

ATG101 (HGNC:25679): (autophagy related 101) Enables identical protein binding activity. Involved in autophagosome assembly. Located in phagophore assembly site. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13056117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG101	NM_021934.5	c.245A>C	p.Glu82Ala	missense_variant	3/4	ENST00000336854.9
ATG101	NM_001098673.2	c.245A>C	p.Glu82Ala	missense_variant	3/4
ATG101	XM_024449120.2	c.245A>C	p.Glu82Ala	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG101	ENST00000336854.9	c.245A>C	p.Glu82Ala	missense_variant	3/4	1	NM_021934.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249486 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1316746 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 655010

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: 9.97e-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	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.019	T;.;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.86	D;T;D;D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.030	N;.;.;.
MutationTaster	Benign	1.0	D
PROVEAN	Benign	0.53	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.76	T;T;T;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.012	B;.;.;.
Vest4		0.19
MutPred		0.39		Gain of catalytic residue at K84 (P = 0.0116);Gain of catalytic residue at K84 (P = 0.0116);Gain of catalytic residue at K84 (P = 0.0116);Gain of catalytic residue at K84 (P = 0.0116);
MVP		0.093
MPC		0.57
ClinPred		0.24	T
GERP RS		3.3
Varity_R		0.41
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: rs754417547; hg19: chr12-52467679;