rs750942616

Variant names:

• chr7-36513260-C-A
• rs750942616
• NM_001637.4:c.1720G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-36513260-C-A
• chr7-36513260-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001637.4(AOAH):​c.1720G>T​(p.Gly574Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G574R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AOAH NM_001637.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOAH	NM_001637.4	c.1720G>T	p.Gly574Trp	missense_variant	Exon 21 of 21	ENST00000617537.5	NP_001628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOAH	ENST00000617537.5	c.1720G>T	p.Gly574Trp	missense_variant	Exon 21 of 21	1	NM_001637.4	ENSP00000483783.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Pathogenic	0.88	D
PhyloP100		4.0
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.86
MutPred		0.54		.;Gain of solvent accessibility (P = 0.0062);
MVP		0.49
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.86
Mutation Taster		=56/44	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: rs750942616; hg19: chr7-36552866;