8-81283960-G-C

Position:

• chr8-81283960-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001444.3(FABP5):​c.340G>C​(p.Gly114Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FABP5 NM_001444.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83

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]

FABP5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP5	NM_001444.3	c.340G>C	p.Gly114Arg	missense_variant	3/4	ENST00000297258.11	NP_001435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP5	ENST00000297258.11	c.340G>C	p.Gly114Arg	missense_variant	3/4	1	NM_001444.3	ENSP00000297258.6
FABP5	ENST00000396359.1	c.238G>C	p.Gly80Arg	missense_variant	3/4	5		ENSP00000379647.1
FABP5	ENST00000481695.1	n.301G>C		non_coding_transcript_exon_variant	2/2	2
FABP5	ENST00000486269.1	n.*20G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455252 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.35	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		1.0	D;.
Vest4		0.80
MutPred		0.69		Gain of MoRF binding (P = 0.0393);.;
MVP		0.75
MPC		0.061
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.90

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

Other links and lift over

dbSNP: rs75108814; hg19: chr8-82196195;