7-36540360-G-C

Variant names:

• chr7-36540360-G-C
• rs550416911
• NM_001637.4:c.1265C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001637.4(AOAH):​c.1265C>G​(p.Thr422Ser) 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. 13/18 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. T422N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AOAH NM_001637.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08633262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOAH	NM_001637.4	c.1265C>G	p.Thr422Ser	missense_variant	Exon 16 of 21	ENST00000617537.5	NP_001628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOAH	ENST00000617537.5	c.1265C>G	p.Thr422Ser	missense_variant	Exon 16 of 21	1	NM_001637.4	ENSP00000483783.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.59
DEOGEN2	Benign	0.032	.;T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-0.94	T
PhyloP100		0.78
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0090	.;B;.
Vest4		0.26
MutPred		0.54		.;Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.12
ClinPred		0.033	T
GERP RS		-1.0
Varity_R		0.16
gMVP		0.45
Mutation Taster		=97/3	polymorphism

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: rs550416911; hg19: chr7-36579966;