NM_033388.2:c.125A>C

Variant names:

• chr11-72816734-A-C
• NM_033388.2:c.125A>C

Variant summary

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

The NM_033388.2(ATG16L2):​c.125A>C​(p.His42Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

Genes affected

ATG16L2 (HGNC:25464): (autophagy related 16 like 2) Predicted to be involved in autophagosome assembly and negative stranded viral RNA replication. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24619505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG16L2	NM_033388.2	c.125A>C	p.His42Pro	missense_variant	Exon 2 of 18	ENST00000321297.10	NP_203746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG16L2	ENST00000321297.10	c.125A>C	p.His42Pro	missense_variant	Exon 2 of 18	1	NM_033388.2	ENSP00000326340.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461692 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727176

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.052	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.025	D;D
Sift4G	Benign	0.062	T;T
Polyphen		0.17	B;P
Vest4		0.52
MutPred		0.54		Gain of ubiquitination at K46 (P = 0.0519);Gain of ubiquitination at K46 (P = 0.0519);
MVP		0.44
MPC		0.75
ClinPred		0.58	D
GERP RS		-2.3
Varity_R		0.42
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-72527779;