12-52076921-G-T

Variant names:

• chr12-52076921-G-T
• rs1279564424
• NM_021934.5:c.388G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021934.5(ATG101):​c.388G>T​(p.Ala130Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.0000014 (0 hom.)
• Consequence: ATG101 NM_021934.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78
• Publications: 0 publications found

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]

ENSG00000257663 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07567927).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021934.5. 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
	ATG101	NM_021934.5	MANE Select	c.388G>T	p.Ala130Ser	missense	Exon 4 of 4	NP_068753.2
	ATG101	NM_001098673.2		c.388G>T	p.Ala130Ser	missense	Exon 4 of 4	NP_001092143.1	Q9BSB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG101	ENST00000336854.9	TSL:1 MANE Select	c.388G>T	p.Ala130Ser	missense	Exon 4 of 4	ENSP00000338990.4	Q9BSB4
	ATG101	ENST00000908677.1		c.388G>T	p.Ala130Ser	missense	Exon 3 of 3	ENSP00000578736.1
	ATG101	ENST00000908678.1		c.388G>T	p.Ala130Ser	missense	Exon 3 of 3	ENSP00000578737.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251440 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

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	Benign	0.059
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		3.8
PROVEAN	Benign	0.86	N
REVEL	Benign	0.073
Sift	Benign	0.70	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.029
MutPred		0.28		Gain of catalytic residue at K125 (P = 0.0062)
MVP		0.068
MPC		0.47
ClinPred		0.35	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.15
Mutation Taster		=98/2	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: rs1279564424; hg19: chr12-52470705;