Variant X-57331630-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_174912.4(FAAH2):c.445C>T(p.Arg149Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,209,583 control chromosomes in the GnomAD database, including 1 homozygotes. There are 79 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00022 ( 1 hom. 71 hem. )

Consequence

FAAH2
NM_174912.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.693

Variant links:

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 links:

FAAH2 (HGNC:):

FAAH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07360852).

BP6

Variant X-57331630-C-T is Benign according to our data. Variant chrX-57331630-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660715.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH2	NM_174912.4 linkuse as main transcript	c.445C>T	p.Arg149Cys	missense_variant	4/11	ENST00000374900.5	NP_777572.2	Q6GMR7B2C6G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAH2	ENST00000374900.5 linkuse as main transcript	c.445C>T	p.Arg149Cys	missense_variant	4/11	1	NM_174912.4	ENSP00000364035.4		Q6GMR7

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111787

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

33973

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000956

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000169

AC:

AN:

183001

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67597

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00108

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000223

AC:

245

AN:

1097742

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

363154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00563

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000170

AC:

AN:

111841

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

34037

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000955

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

FAAH2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.011

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.12

Sift

Uncertain

0.0010

Sift4G

Benign

0.10

Polyphen

0.037

Vest4

0.62

MVP

0.56

MPC

0.00072

ClinPred

0.22

GERP RS

2.4

Varity_R

0.41

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over