dbSNP rs2241880: ATG16L1:p.Thr300Pro (chr2-233274722-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363742.2(ATG16L1):c.949A>C(p.Thr317Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T317A) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATG16L1
NM_001363742.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.448

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050829947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363742.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATG16L1	NM_030803.7	MANE Select	c.898A>C	p.Thr300Pro	missense	Exon 9 of 18	NP_110430.5
ATG16L1	NM_001363742.2		c.949A>C	p.Thr317Pro	missense	Exon 10 of 19	NP_001350671.1
ATG16L1	NM_017974.4		c.841A>C	p.Thr281Pro	missense	Exon 8 of 17	NP_060444.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.898A>C	p.Thr300Pro	missense	Exon 9 of 18	ENSP00000375872.4
ATG16L1	ENST00000392020.8	TSL:1	c.841A>C	p.Thr281Pro	missense	Exon 8 of 17	ENSP00000375875.4
ATG16L1	ENST00000347464.9	TSL:1	c.409A>C	p.Thr137Pro	missense	Exon 5 of 14	ENSP00000318259.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726372

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110420

Other (OTH)

AF:

0.00

AC:

AN:

60326

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.7

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.041

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.082

M_CAP

Benign

0.014

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-0.45

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.18

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.082

MutPred

0.20

Loss of phosphorylation at T300 (P = 0.0722)

MVP

0.74

MPC

0.74

ClinPred

0.077

GERP RS

-11

Varity_R

0.18

gMVP

0.36

Mutation Taster

=79/21

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over