chr1-31369402-C-T

Variant names:

• chr1-31369402-C-T
• NM_004102.5:c.229G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004102.5(FABP3):​c.229G>A​(p.Asp77Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: FABP3 NM_004102.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP3	NM_004102.5	c.229G>A	p.Asp77Asn	missense_variant	Exon 2 of 4	ENST00000373713.7	NP_004093.1
FABP3	NM_001320996.2	c.262G>A	p.Asp88Asn	missense_variant	Exon 2 of 4		NP_001307925.1
FABP3	XM_011541007.4	c.229G>A	p.Asp77Asn	missense_variant	Exon 2 of 4		XP_011539309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP3	ENST00000373713.7	c.229G>A	p.Asp77Asn	missense_variant	Exon 2 of 4	1	NM_004102.5	ENSP00000362817.2
FABP3	ENST00000482018.1	c.229G>A	p.Asp77Asn	missense_variant	Exon 4 of 6	5		ENSP00000473982.1
FABP3	ENST00000497275.5	n.189G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
FABP3	ENST00000498148.5	n.229G>A		non_coding_transcript_exon_variant	Exon 2 of 5	2		ENSP00000474078.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229G>A (p.D77N) alteration is located in exon 2 (coding exon 2) of the FABP3 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the aspartic acid (D) at amino acid position 77 to be replaced by an asparagine (N). 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	0.95
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	4.3	H;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.8	D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0040	D;.
Polyphen		0.99	D;.
Vest4		0.72
MutPred		0.69		Loss of ubiquitination at K80 (P = 0.0331);Loss of ubiquitination at K80 (P = 0.0331);
MVP		0.86
MPC		0.26
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.93
gMVP		0.93

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: chr1-31842249;