1-31365893-T-G

Position:

• chr1-31365893-T-G

Variant summary

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

The NM_004102.5(FABP3):​c.395A>C​(p.Glu132Ala) 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: 31)
• Consequence: FABP3 NM_004102.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41

Genes affected

FABP3 (HGNC:3557): (fatty acid binding protein 3) The intracellular fatty acid-binding proteins (FABPs) belongs to a multigene family. FABPs are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. They form 14-15 kDa proteins and are thought to participate in the uptake, intracellular metabolism and/or transport of long-chain fatty acids. They may also be responsible in the modulation of cell growth and proliferation. Fatty acid-binding protein 3 gene contains four exons and its function is to arrest growth of mammary epithelial cells. This gene is a candidate tumor suppressor gene for human breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

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=0.15425098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FABP3	NM_004102.5	c.395A>C	p.Glu132Ala	missense_variant	4/4	ENST00000373713.7
FABP3	NM_001320996.2	c.428A>C	p.Glu143Ala	missense_variant	4/4
FABP3	XM_011541007.4	c.348+1500A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP3	ENST00000373713.7	c.395A>C	p.Glu132Ala	missense_variant	4/4	1	NM_004102.5	P1
FABP3	ENST00000482018.1	c.395A>C	p.Glu132Ala	missense_variant	6/6	5
FABP3	ENST00000497275.5	n.355A>C		non_coding_transcript_exon_variant	3/3	2
FABP3	ENST00000498148.5	c.*192A>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

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 02, 2023

The c.395A>C (p.E132A) alteration is located in exon 4 (coding exon 4) of the FABP3 gene. This alteration results from a A to C substitution at nucleotide position 395, causing the glutamic acid (E) at amino acid position 132 to be replaced by an alanine (A). 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	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.77	T;D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.53	N;.
MutationTaster	Benign	0.88	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.79	N;.
REVEL	Benign	0.035
Sift	Benign	0.089	T;.
Sift4G	Uncertain	0.016	D;.
Polyphen		0.0010	B;.
Vest4		0.16
MutPred		0.45		Gain of ubiquitination at K131 (P = 0.0624);Gain of ubiquitination at K131 (P = 0.0624);
MVP		0.39
MPC		0.13
ClinPred		0.21	T
GERP RS		1.6
Varity_R		0.17
gMVP		0.57

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: rs1640099352; hg19: chr1-31838740;