Genetic Variant FABP9:p.Ala30Thr (chr8-81459323-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080526.2(FABP9):c.88G>A(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000458 in 1,528,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

FABP9
NM_001080526.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.273

Variant links:

Genes affected

FABP9 (HGNC:3563): (fatty acid binding protein 9) Predicted to enable lipid binding activity. Predicted to be involved in acrosome assembly. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FABP9 links:

ENSG00000253859 (HGNC:):

ENSG00000253859 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07122317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP9	NM_001080526.2 link	c.88G>A	p.Ala30Thr	missense_variant	Exon 2 of 4	ENST00000379071.4	NP_001073995.1	Q0Z7S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP9	ENST00000379071.4 link	c.88G>A	p.Ala30Thr	missense_variant	Exon 2 of 4	2	NM_001080526.2	ENSP00000368362.2		Q0Z7S8
ENSG00000253859	ENST00000524085.2 link	n.298+19230C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1376674

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

682180

show subpopulations

Gnomad4 AFR exome

AF:

0.000146

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:

0.0000176

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88G>A (p.A30T) alteration is located in exon 2 (coding exon 2) of the FABP9 gene. This alteration results from a G to A substitution at nucleotide position 88, causing the alanine (A) at amino acid position 30 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

0.079

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0040

DANN

Benign

0.62

DEOGEN2

Benign

0.022

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.53

M_CAP

Benign

0.0031

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

2.6

REVEL

Benign

0.019

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.14

MutPred

0.47

Loss of methylation at R31 (P = 0.0724);

MVP

0.099

MPC

0.035

ClinPred

0.068

GERP RS

-6.2

Varity_R

0.093

gMVP

0.32

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

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