8-81461506-C-A

Variant names:

• chr8-81461506-C-A
• rs755752591
• NM_001080526.2:c.18G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080526.2(FABP9):​c.18G>T​(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 32)
• Consequence: FABP9 NM_001080526.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 0 publications found

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]

LOC101927118 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39313638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080526.2. 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
	FABP9	NM_001080526.2	MANE Select	c.18G>T	p.Leu6Phe	missense	Exon 1 of 4	NP_001073995.1	Q0Z7S8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FABP9	ENST00000379071.4	TSL:2 MANE Select	c.18G>T	p.Leu6Phe	missense	Exon 1 of 4	ENSP00000368362.2	Q0Z7S8
	ENSG00000253374	ENST00000524085.2	TSL:5	n.298+21413C>A		intron	N/A
	ENSG00000253374	ENST00000832857.1		n.326+21413C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.054
Eigen_PC	Benign	-0.0012
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.0020
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.067
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.044	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.26		Gain of ubiquitination at K10 (P = 0.0913)
MVP		0.30
MPC		0.047
ClinPred		0.92	D
GERP RS		3.5
PromoterAI		0.024	Neutral
Varity_R		0.34
gMVP		0.46
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs755752591; hg19: chr8-82373741; COSMIC: COSV66911896;