chr8-81529467-C-G

Position:

• chr8-81529467-C-G

Variant summary

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

The NM_001105281.6(FABP12):​c.217G>C​(p.Glu73Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.04

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP12	NM_001105281.6	c.217G>C	p.Glu73Gln	missense_variant	3/5		NP_001098751.1
FABP12	XM_006716465.4	c.217G>C	p.Glu73Gln	missense_variant	3/5		XP_006716528.1
FABP12	XM_011517577.3	c.217G>C	p.Glu73Gln	missense_variant	4/6		XP_011515879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP12	ENST00000360464.6	c.217G>C	p.Glu73Gln	missense_variant	3/5	1		ENSP00000353650.4
FABP12	ENST00000692030.1	c.217G>C	p.Glu73Gln	missense_variant	4/6			ENSP00000510293.1
FABP12	ENST00000519696.1	n.169G>C		non_coding_transcript_exon_variant	2/4	5		ENSP00000427973.1
ENSG00000253374	ENST00000523380.5	n.505+3011C>G		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

Sep 16, 2021

The c.217G>C (p.E73Q) alteration is located in exon 2 (coding exon 2) of the FABP12 gene. This alteration results from a G to C substitution at nucleotide position 217, causing the glutamic acid (E) at amino acid position 73 to be replaced by a glutamine (Q). 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	0.31
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.81		Gain of sheet (P = 0.0827);
MVP		0.092
MPC		0.060
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.61
gMVP		0.70

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: chr8-82441702;