Variant 1-31372998-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004102.5(FABP3):c.17T>C(p.Leu6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

FABP3
NM_004102.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.782

Variant links:

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]

FABP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36088735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP3	NM_004102.5 linkuse as main transcript	c.17T>C	p.Leu6Pro	missense_variant	1/4	ENST00000373713.7	NP_004093.1	P05413A0A384MDY5
FABP3	NM_001320996.2 linkuse as main transcript	c.17T>C	p.Leu6Pro	missense_variant	1/4		NP_001307925.1
FABP3	XM_011541007.4 linkuse as main transcript	c.17T>C	p.Leu6Pro	missense_variant	1/4		XP_011539309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FABP3	ENST00000373713.7 linkuse as main transcript	c.17T>C	p.Leu6Pro	missense_variant	1/4	1	NM_004102.5	ENSP00000362817.2	P05413
FABP3	ENST00000482018.1 linkuse as main transcript	c.17T>C	p.Leu6Pro	missense_variant	3/6	5		ENSP00000473982.1	S4R371
FABP3	ENST00000498148.5 linkuse as main transcript	n.17T>C		non_coding_transcript_exon_variant	1/5	2		ENSP00000474078.1	S4R3A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251130

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.17T>C (p.L6P) alteration is located in exon 1 (coding exon 1) of the FABP3 gene. This alteration results from a T to C substitution at nucleotide position 17, causing the leucine (L) at amino acid position 6 to be replaced by a proline (P). 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

0.72

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.079

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.1

D;.

REVEL

Benign

0.071

Sift

Uncertain

0.020

D;.

Sift4G

Uncertain

0.039

D;.

Polyphen

0.61

P;.

Vest4

0.25

MutPred

0.35

Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);

MVP

0.37

MPC

0.46

ClinPred

0.90

GERP RS

-0.063

Varity_R

0.80

gMVP

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over