X-57448667-GCA-TCG

Variant names:

• chrX-57448667-GCA-TCG
• NM_174912.4:c.1372_1374delGCAinsTCG
• FAAH2 p.Ala458Ser

Variant summary

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

The NM_174912.4(FAAH2):​c.1372_1374delGCAinsTCG​(p.Ala458Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAAH2 NM_174912.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50
• Publications: 0 publications found

Genes affected

FAAH2 (HGNC:26440): (fatty acid amide hydrolase 2) This gene encodes a fatty acid amide hydrolase that shares a conserved protein motif with the amidase signature family of enzymes. The encoded enzyme is able to catalyze the hydrolysis of a broad range of bioactive lipids, including those from the three main classes of fatty acid amides; N-acylethanolamines, fatty acid primary amides and N-acyl amino acids. This enzyme has a preference for monounsaturated acyl chains as a substrate. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

FAAH2 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174912.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	NM_174912.4	MANE Select	c.1372_1374delGCAinsTCG	p.Ala458Ser	missense	N/A	NP_777572.2	Q6GMR7
	FAAH2	NM_001353840.1		c.1252_1254delGCAinsTCG	p.Ala418Ser	missense	N/A	NP_001340769.1
	FAAH2	NM_001353841.1		c.1162_1164delGCAinsTCG	p.Ala388Ser	missense	N/A	NP_001340770.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	ENST00000374900.5	TSL:1 MANE Select	c.1372_1374delGCAinsTCG	p.Ala458Ser	missense	N/A	ENSP00000364035.4	Q6GMR7
	FAAH2	ENST00000491179.1	TSL:1	n.51-15_51-13delGCAinsTCG		intron	N/A
	FAAH2	ENST00000886040.1		c.1399_1401delGCAinsTCG	p.Ala467Ser	missense	N/A	ENSP00000556099.1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-57475100;