Variant chr2-233256112-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_030803.7(ATG16L1):c.126G>T(p.Leu42Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ATG16L1
NM_030803.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.731

Variant links:

Genes affected

ATG16L1 (HGNC:21498): (autophagy related 16 like 1) The protein encoded by this gene is part of a large protein complex that is necessary for autophagy, the major process by which intracellular components are targeted to lysosomes for degradation. Defects in this gene are a cause of susceptibility to inflammatory bowel disease type 10 (IBD10). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

ATG16L1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG16L1	NM_030803.7 linkuse as main transcript	c.126G>T	p.Leu42Phe	missense_variant	2/18	ENST00000392017.9	NP_110430.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG16L1	ENST00000392017.9 linkuse as main transcript	c.126G>T	p.Leu42Phe	missense_variant	2/18	1	NM_030803.7	ENSP00000375872	P3	Q676U5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249186

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000389

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:

0.00000342

AC:

AN:

1461416

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.126G>T (p.L42F) alteration is located in exon 2 (coding exon 2) of the ATG16L1 gene. This alteration results from a G to T substitution at nucleotide position 126, causing the leucine (L) at amino acid position 42 to be replaced by a phenylalanine (F). 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

Pathogenic

0.87

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;T;T;.;T;.;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.89

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.68

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.1

M;M;.;M;.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.9

N;D;D;N;D;D;N;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0090

D;D;D;D;.;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D;D

Polyphen

1.0

.;D;.;D;.;.;D;.

Vest4

0.69

MutPred

0.79

Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);Gain of methylation at K41 (P = 0.0263);

MVP

0.84

MPC

1.6

ClinPred

0.63

GERP RS

4.8

Varity_R

0.35

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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