8-81459261-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080526.2(FABP9):​c.150G>A​(p.Met50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000042 in 1,429,248 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M50T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

FABP9
NM_001080526.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033615112).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FABP9NM_001080526.2 linkc.150G>A p.Met50Ile 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
FABP9ENST00000379071.4 linkc.150G>A p.Met50Ile missense_variant Exon 2 of 4 2 NM_001080526.2 ENSP00000368362.2 Q0Z7S8
ENSG00000253859ENST00000524085.2 linkn.298+19168C>T intron_variant Intron 2 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000420
AC:
6
AN:
1429248
Hom.:
0
Cov.:
31
AF XY:
0.00000704
AC XY:
5
AN XY:
710476
show subpopulations
Gnomad4 AFR exome
AF:
0.000131
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:
0.0000338
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.150G>A (p.M50I) 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 150, causing the methionine (M) at amino acid position 50 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.12
DANN
Benign
0.65
DEOGEN2
Benign
0.022
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.33
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
1.8
N
REVEL
Benign
0.080
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.20
MutPred
0.36
Loss of disorder (P = 0.0726);
MVP
0.12
MPC
0.038
ClinPred
0.063
T
GERP RS
0.83
Varity_R
0.16
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs768295290; hg19: chr8-82371496; API