8-81459323-C-A

Variant names:

• chr8-81459323-C-A
• rs904186932
• NM_001080526.2:c.88G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080526.2(FABP9):​c.88G>T​(p.Ala30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A30T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FABP9 NM_001080526.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15385184).

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.88G>T	p.Ala30Ser	missense	Exon 2 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.88G>T	p.Ala30Ser	missense	Exon 2 of 4	ENSP00000368362.2	Q0Z7S8
	ENSG00000253374	ENST00000524085.2	TSL:5	n.298+19230C>A		intron	N/A
	ENSG00000253374	ENST00000832857.1		n.326+19230C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376672 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682178

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27472

American (AMR) AF: 0.00 AC: 0 AN: 24820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23350

East Asian (EAS) AF: 0.00 AC: 0 AN: 34104

South Asian (SAS) AF: 0.00 AC: 0 AN: 70672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081158

Other (OTH) AF: 0.00 AC: 0 AN: 56888

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.021
DANN	Benign	0.84
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.71	N
PhyloP100		-0.27
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.017
Sift	Benign	0.16	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.49		Loss of methylation at R31 (P = 0.0817)
MVP		0.14
MPC		0.045
ClinPred		0.13	T
GERP RS		-6.2
Varity_R		0.17
gMVP		0.34
Mutation Taster		=99/1	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: rs904186932; hg19: chr8-82371558;