8-81527085-C-G

Position:

• chr8-81527085-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105281.6(FABP12):​c.283G>C​(p.Val95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FABP12 NM_001105281.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50

Genes affected

FABP12 (HGNC:34524): (fatty acid binding protein 12) Predicted to enable lipid binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FABP12 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24482575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP12	NM_001105281.6	c.283G>C	p.Val95Leu	missense_variant	4/5		NP_001098751.1
FABP12	XM_006716465.4	c.283G>C	p.Val95Leu	missense_variant	4/5		XP_006716528.1
FABP12	XM_011517577.3	c.283G>C	p.Val95Leu	missense_variant	5/6		XP_011515879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP12	ENST00000360464.6	c.283G>C	p.Val95Leu	missense_variant	4/5	1		ENSP00000353650.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.283G>C (p.V95L) alteration is located in exon 3 (coding exon 3) of the FABP12 gene. This alteration results from a G to C substitution at nucleotide position 283, causing the valine (V) at amino acid position 95 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.051
Sift	Benign	0.19	T
Sift4G	Benign	0.22	T
Polyphen		0.0060	B
Vest4		0.61
MutPred		0.43		Gain of disorder (P = 0.1862);
MVP		0.014
MPC		0.017
ClinPred		0.16	T
GERP RS		1.3
Varity_R		0.12
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-82439320;