8-81527073-C-A

Position:

• chr8-81527073-C-A

Variant summary

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

The NM_001105281.6(FABP12):​c.295G>T​(p.Asp99Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FABP12 NM_001105281.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.434

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]

ENSG00000253374 (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.295G>T	p.Asp99Tyr	missense_variant	4/5		NP_001098751.1
FABP12	XM_006716465.4	c.295G>T	p.Asp99Tyr	missense_variant	4/5		XP_006716528.1
FABP12	XM_011517577.3	c.295G>T	p.Asp99Tyr	missense_variant	5/6		XP_011515879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP12	ENST00000360464.6	c.295G>T	p.Asp99Tyr	missense_variant	4/5	1		ENSP00000353650.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460214 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Oct 07, 2024

The c.295G>T (p.D99Y) alteration is located in exon 3 (coding exon 3) of the FABP12 gene. This alteration results from a G to T substitution at nucleotide position 295, causing the aspartic acid (D) at amino acid position 99 to be replaced by a tyrosine (Y). 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	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.5	M
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.88	P
Vest4		0.55
MutPred		0.53		Loss of disorder (P = 0.0165);
MVP		0.18
MPC		0.039
ClinPred		0.90	D
GERP RS		-2.3
Varity_R		0.42
gMVP		0.72

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: rs752950072; hg19: chr8-82439308;