8-81458636-A-T

Variant names:

• chr8-81458636-A-T
• rs200298497
• NM_001080526.2:c.314T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001080526.2(FABP9):​c.314T>A​(p.Ile105Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. I105T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: FABP9 NM_001080526.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.60
• 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]

ENSG00000253374 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

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.314T>A	p.Ile105Asn	missense	Exon 3 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.314T>A	p.Ile105Asn	missense	Exon 3 of 4	ENSP00000368362.2	Q0Z7S8
	ENSG00000253374	ENST00000524085.2	TSL:5	n.298+18543A>T		intron	N/A
	ENSG00000253374	ENST00000832857.1		n.326+18543A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461404 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727004

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111772

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		6.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.76		Gain of disorder (P = 0.0195)
MVP		0.32
MPC		0.31
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.93
gMVP		0.93
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200298497; hg19: chr8-82370871;