rs1051231

Variant names:

• chr8-81479452-T-G
• rs1051231
• NM_001442.3:c.310A>C

Variant summary

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

The NM_001442.3(FABP4):​c.310A>C​(p.Thr104Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T104I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FABP4 NM_001442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 3 publications found

Genes affected

FABP4 (HGNC:3559): (fatty acid binding protein 4) FABP4 encodes the fatty acid binding protein found in adipocytes. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. [provided by RefSeq, Jul 2008]

FABP4 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000253374 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001442.3. 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
	FABP4	NM_001442.3	MANE Select	c.310A>C	p.Thr104Pro	missense	Exon 3 of 4	NP_001433.1	P15090

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FABP4	ENST00000256104.5	TSL:1 MANE Select	c.310A>C	p.Thr104Pro	missense	Exon 3 of 4	ENSP00000256104.4	P15090
	FABP4	ENST00000956908.1		c.310A>C	p.Thr104Pro	missense	Exon 3 of 4	ENSP00000626967.1
	FABP4	ENST00000956910.1		c.307A>C	p.Thr103Pro	missense	Exon 3 of 4	ENSP00000626969.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.0
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.43
MutPred		0.54		Loss of phosphorylation at T104 (P = 0.0348)
MVP		0.70
MPC		0.82
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.96
gMVP		0.94
Mutation Taster		=46/54	disease causing

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: rs1051231; hg19: chr8-82391687;