8-81284554-A-C

Variant names:

• chr8-81284554-A-C
• rs776920520
• NM_001444.3:c.395A>C

Variant summary

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

The NM_001444.3(FABP5):​c.395A>C​(p.Glu132Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E132V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FABP5 NM_001444.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17
• Publications: 0 publications found

Genes affected

FABP5 (HGNC:3560): (fatty acid binding protein 5) This gene encodes the fatty acid binding protein found in epidermal cells, and was first identified as being upregulated in psoriasis tissue. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. FABPs may play roles in fatty acid uptake, transport, and metabolism. Polymorphisms in this gene are associated with type 2 diabetes. The human genome contains many pseudogenes similar to this locus.[provided by RefSeq, Feb 2011]

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=0.41695794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001444.3. 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
	FABP5	NM_001444.3	MANE Select	c.395A>C	p.Glu132Ala	missense	Exon 4 of 4	NP_001435.1	Q01469

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FABP5	ENST00000297258.11	TSL:1 MANE Select	c.395A>C	p.Glu132Ala	missense	Exon 4 of 4	ENSP00000297258.6	Q01469
	FABP5	ENST00000943582.1		c.392A>C	p.Glu131Ala	missense	Exon 4 of 4	ENSP00000613641.1
	FABP5	ENST00000943583.1		c.392A>C	p.Glu131Ala	missense	Exon 4 of 4	ENSP00000613642.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440798 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 718072

African (AFR) AF: 0.00 AC: 0 AN: 33108

American (AMR) AF: 0.00 AC: 0 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 85784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096600

Other (OTH) AF: 0.00 AC: 0 AN: 59756

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.50	T
PhyloP100		5.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.041	D
Polyphen		0.96	D
Vest4		0.25
MutPred		0.57		Gain of MoRF binding (P = 0.0333)
MVP		0.71
MPC		0.050
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.55
gMVP		0.81
Mutation Taster		=42/58	disease causing

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: rs776920520; hg19: chr8-82196789;