8-81529458-G-A

Position:

• chr8-81529458-G-A

Variant summary

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

The NM_001105281.6(FABP12):​c.226C>T​(p.Pro76Ser) 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: 33)
• Consequence: FABP12 NM_001105281.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.786

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080797374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP12	NM_001105281.6	c.226C>T	p.Pro76Ser	missense_variant	3/5		NP_001098751.1
FABP12	XM_006716465.4	c.226C>T	p.Pro76Ser	missense_variant	3/5		XP_006716528.1
FABP12	XM_011517577.3	c.226C>T	p.Pro76Ser	missense_variant	4/6		XP_011515879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP12	ENST00000360464.6	c.226C>T	p.Pro76Ser	missense_variant	3/5	1		ENSP00000353650.4
FABP12	ENST00000692030.1	c.226C>T	p.Pro76Ser	missense_variant	4/6			ENSP00000510293.1
FABP12	ENST00000519696.1	n.178C>T		non_coding_transcript_exon_variant	2/4	5		ENSP00000427973.1
ENSG00000253374	ENST00000523380.5	n.505+3002G>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 15, 2024

The c.226C>T (p.P76S) alteration is located in exon 2 (coding exon 2) of the FABP12 gene. This alteration results from a C to T substitution at nucleotide position 226, causing the proline (P) at amino acid position 76 to be replaced by a serine (S). 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	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.58
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.039
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.042	D
Polyphen		0.11	B
Vest4		0.12
MutPred		0.44		Gain of glycosylation at P76 (P = 0.0308);
MVP		0.030
MPC		0.015
ClinPred		0.17	T
GERP RS		1.0
Varity_R		0.042
gMVP		0.37

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: rs1809001053; hg19: chr8-82441693;