5-160232245-T-C

Position:

• chr5-160232245-T-C

Variant summary

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

The NM_001445.3(FABP6):​c.215T>C​(p.Ile72Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FABP6 NM_001445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.16

Genes affected

FABP6 (HGNC:3561): (fatty acid binding protein 6) This gene encodes the ileal fatty acid binding protein. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. FABP6 and FABP1 (the liver fatty acid binding protein) are also able to bind bile acids. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. Transcript variants generated by alternate transcription promoters and/or alternate splicing have been found for this gene. [provided by RefSeq, Jul 2008]

FABP6 (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=0.22629735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP6	NM_001445.3	c.215T>C	p.Ile72Thr	missense_variant	2/4	ENST00000402432.4	NP_001436.1
FABP6	NM_001040442.1	c.362T>C	p.Ile121Thr	missense_variant	4/6		NP_001035532.1
FABP6	NM_001130958.2	c.362T>C	p.Ile121Thr	missense_variant	5/7		NP_001124430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP6	ENST00000402432.4	c.215T>C	p.Ile72Thr	missense_variant	2/4	1	NM_001445.3	ENSP00000385433.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

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

Oct 08, 2024

The c.362T>C (p.I121T) alteration is located in exon 4 (coding exon 4) of the FABP6 gene. This alteration results from a T to C substitution at nucleotide position 362, causing the isoleucine (I) at amino acid position 121 to be replaced by a threonine (T). 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.84	P;B
Vest4		0.36
MutPred		0.49		.;Gain of disorder (P = 0.013);
MVP		0.28
MPC		0.63
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.75
gMVP		0.47

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: rs1760404792; hg19: chr5-159659252;