7-36549445-A-G

Variant summary

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

The NM_001637.4(AOAH):c.1052T>C(p.Ile351Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AOAH NM_001637.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

Genes affected

AOAH (HGNC:548): (acyloxyacyl hydrolase) This locus encodes both the light and heavy subunits of acyloxyacyl hydrolase. The encoded enzyme catalyzes the hydrolysis of acyloxylacyl-linked fatty acyl chains from bacterial lipopolysaccharides, effectively detoxifying these molecules. The encoded protein may play a role in modulating host inflammatory response to gram-negative bacteria. Alternatively spliced transcript variants have been described.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOAH	NM_001637.4	c.1052T>C	p.Ile351Thr	missense_variant	14/21	ENST00000617537.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOAH	ENST00000617537.5	c.1052T>C	p.Ile351Thr	missense_variant	14/21	1	NM_001637.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443750 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 718628

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Dec 02, 2021

The c.1052T>C (p.I351T) alteration is located in exon 14 (coding exon 14) of the AOAH gene. This alteration results from a T to C substitution at nucleotide position 1052, causing the isoleucine (I) at amino acid position 351 to be replaced by a threonine (T). 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	0.081
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
Cadd	Benign	23
Dann	Uncertain	0.98
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.94	D;D;D;D
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.055	T;D;D
Polyphen		0.065	.;B;.
Vest4		0.64
MutPred		0.71		.;Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);
MVP		0.24
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.49
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-36589051;