chr2-233281126-C-T

Variant names:

• chr2-233281126-C-T
• rs1359314594
• NM_030803.7:c.1082C>T

Variant summary

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

The NM_030803.7(ATG16L1):​c.1082C>T​(p.Ser361Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030803.7. 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
	ATG16L1	NM_030803.7	MANE Select	c.1082C>T	p.Ser361Phe	missense	Exon 11 of 18	NP_110430.5
	ATG16L1	NM_001363742.2		c.1133C>T	p.Ser378Phe	missense	Exon 12 of 19	NP_001350671.1	E7EVC7
	ATG16L1	NM_017974.4		c.1025C>T	p.Ser342Phe	missense	Exon 10 of 17	NP_060444.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.1082C>T	p.Ser361Phe	missense	Exon 11 of 18	ENSP00000375872.4	Q676U5-1
	ATG16L1	ENST00000392020.8	TSL:1	c.1025C>T	p.Ser342Phe	missense	Exon 10 of 17	ENSP00000375875.4	Q676U5-2
	ATG16L1	ENST00000347464.9	TSL:1	c.593C>T	p.Ser198Phe	missense	Exon 7 of 14	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 241156 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000316

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.89e-7 AC: 1 AN: 1451038 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 721834

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.0000239 AC: 1 AN: 41772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39412

South Asian (SAS) AF: 0.00 AC: 0 AN: 83378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108864

Other (OTH) AF: 0.00 AC: 0 AN: 59904

GnomAD4 genome Cov.: 33

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	0.22
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.46		Loss of disorder (P = 0.0076)
MVP		0.61
MPC		0.63
ClinPred		0.51	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.25
Mutation Taster		=27/73	disease causing

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: rs1359314594; hg19: chr2-234189772; COSMIC: COSV105258630; COSMIC: COSV105258630;