chr2-233281118-C-G

Position:

• chr2-233281118-C-G

Variant summary

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

The NM_030803.7(ATG16L1):​c.1074C>G​(p.Phe358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0710

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]

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=0.09946433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG16L1	NM_030803.7	c.1074C>G	p.Phe358Leu	missense_variant	11/18	ENST00000392017.9	NP_110430.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG16L1	ENST00000392017.9	c.1074C>G	p.Phe358Leu	missense_variant	11/18	1	NM_030803.7	ENSP00000375872	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.1017C>G (p.F339L) alteration is located in exon 10 (coding exon 10) of the ATG16L1 gene. This alteration results from a C to G substitution at nucleotide position 1017, causing the phenylalanine (F) at amino acid position 339 to be replaced by a leucine (L). 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	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.015	.;T;.;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.099	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.40	.;N;.;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.37	N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.73	T;T;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.14
MutPred		0.43		.;Loss of sheet (P = 0.0817);.;.;
MVP		0.43
MPC		0.67
ClinPred		0.30	T
GERP RS		2.1
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-234189764;