8-81525077-T-A

Position:

• chr8-81525077-T-A

Variant summary

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

The NM_001105281.6(FABP12):​c.392A>T​(p.Lys131Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: FABP12 NM_001105281.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.224

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP12	NM_001105281.6	c.392A>T	p.Lys131Ile	missense_variant	5/5		NP_001098751.1
FABP12	XM_006716465.4	c.392A>T	p.Lys131Ile	missense_variant	5/5		XP_006716528.1
FABP12	XM_011517577.3	c.392A>T	p.Lys131Ile	missense_variant	6/6		XP_011515879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP12	ENST00000360464.6	c.392A>T	p.Lys131Ile	missense_variant	5/5	1		ENSP00000353650.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

Jan 06, 2023

The c.392A>T (p.K131I) alteration is located in exon 4 (coding exon 4) of the FABP12 gene. This alteration results from a A to T substitution at nucleotide position 392, causing the lysine (K) at amino acid position 131 to be replaced by an isoleucine (I). 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	0.25
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.0026
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.96	D
Vest4		0.39
MutPred		0.66		Loss of ubiquitination at K131 (P = 0.0063);
MVP		0.33
MPC		0.028
ClinPred		1.0	D
GERP RS		2.6
Varity_R		0.77
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1808855047; hg19: chr8-82437312;