1-31369527-C-T

Variant names:

• chr1-31369527-C-T
• rs768005655
• NM_004102.5:c.104G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004102.5(FABP3):​c.104G>A​(p.Ser35Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S35T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FABP3 NM_004102.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023436904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP3	NM_004102.5	c.104G>A	p.Ser35Asn	missense_variant	Exon 2 of 4	ENST00000373713.7	NP_004093.1
FABP3	NM_001320996.2	c.137G>A	p.Ser46Asn	missense_variant	Exon 2 of 4		NP_001307925.1
FABP3	XM_011541007.4	c.104G>A	p.Ser35Asn	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.104G>A	p.Ser35Asn	missense_variant	Exon 2 of 4	1	NM_004102.5	ENSP00000362817.2
FABP3	ENST00000482018.1	c.104G>A	p.Ser35Asn	missense_variant	Exon 4 of 6	5		ENSP00000473982.1
FABP3	ENST00000497275.5	n.64G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
FABP3	ENST00000498148.5	n.104G>A		non_coding_transcript_exon_variant	Exon 2 of 5	2		ENSP00000474078.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251450 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135898

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: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.62
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.53	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.1	N;.
REVEL	Benign	0.020
Sift	Benign	1.0	T;.
Sift4G	Benign	0.88	T;.
Polyphen		0.0	B;.
Vest4		0.025
MutPred		0.28		Loss of ubiquitination at K38 (P = 0.1091);Loss of ubiquitination at K38 (P = 0.1091);
MVP		0.18
MPC		0.11
ClinPred		0.026	T
GERP RS		-8.7
Varity_R		0.091
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs768005655; hg19: chr1-31842374;