Genetic Variant ATG101:p.Arg183Trp (chr12-52077080-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021934.5(ATG101):c.547C>T(p.Arg183Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,614,044 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ATG101
NM_021934.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Variant links:

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]

ATG101 links:

ENSG00000257663 (HGNC:):

ENSG00000257663 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2998752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG101	NM_021934.5 link	c.547C>T	p.Arg183Trp	missense_variant	Exon 4 of 4	ENST00000336854.9	NP_068753.2	Q9BSB4A0A024R128
ATG101	NM_001098673.2 link	c.547C>T	p.Arg183Trp	missense_variant	Exon 4 of 4		NP_001092143.1	Q9BSB4A0A024R128
ATG101	XM_024449120.2 link	c.547C>T	p.Arg183Trp	missense_variant	Exon 5 of 5		XP_024304888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATG101	ENST00000336854.9 link	c.547C>T	p.Arg183Trp	missense_variant	Exon 4 of 4	1	NM_021934.5	ENSP00000338990.4	Q9BSB4
ATG101	ENST00000553049.5 link	c.547C>T	p.Arg183Trp	missense_variant	Exon 4 of 4	2		ENSP00000450088.1	F8VQD9
ENSG00000257663	ENST00000550301.1 link	n.408G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
ATG101	ENST00000548915.1 link	c.*124C>T		downstream_gene_variant		3		ENSP00000449935.1	F8VVA0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251426

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.547C>T (p.R183W) alteration is located in exon 4 (coding exon 2) of the ATG101 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.087

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;.

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.018

D;D

Polyphen

0.0010

B;.

Vest4

0.17

MVP

0.32

MPC

0.54

ClinPred

0.41

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over