Genetic Variant FABP9:p.Thr8Ile (chr8-81461501-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080526.2(FABP9):c.23C>T(p.Thr8Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,613,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

FABP9
NM_001080526.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

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:

LOC101927118 (HGNC:):

LOC101927118 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP9	NM_001080526.2 link	c.23C>T	p.Thr8Ile	missense_variant	Exon 1 of 4	ENST00000379071.4	NP_001073995.1	Q0Z7S8
LOC101927118	XR_001745980.2 link	n.44G>A		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP9	ENST00000379071.4 link	c.23C>T	p.Thr8Ile	missense_variant	Exon 1 of 4	2	NM_001080526.2	ENSP00000368362.2		Q0Z7S8
ENSG00000253859	ENST00000524085.2 link	n.298+21408G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250920

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461446

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000104

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000495

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23C>T (p.T8I) alteration is located in exon 1 (coding exon 1) of the FABP9 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the threonine (T) at amino acid position 8 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

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.23

Sift

Uncertain

0.014

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.35

MVP

0.38

MPC

0.19

ClinPred

0.97

GERP RS

4.4

Varity_R

0.58

gMVP

0.61

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