8-81459261-C-T

Variant names:

• chr8-81459261-C-T
• rs768295290
• NM_001080526.2:c.150G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

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]

ENSG00000253859 (HGNC:):

ACMG classification

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
FABP9	NM_001080526.2	c.150G>A	p.Met50Ile	missense_variant	Exon 2 of 4	ENST00000379071.4	NP_001073995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP9	ENST00000379071.4	c.150G>A	p.Met50Ile	missense_variant	Exon 2 of 4	2	NM_001080526.2	ENSP00000368362.2
ENSG00000253859	ENST00000524085.2	n.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

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

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

Other links and lift over

dbSNP: rs768295290; hg19: chr8-82371496;