Variant 5-160232251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001445.3(FABP6):c.221C>T(p.Thr74Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000683 in 1,610,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

FABP6
NM_001445.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FABP6	NM_001445.3 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	2/4	ENST00000402432.4
FABP6	NM_001040442.1 linkuse as main transcript	c.368C>T	p.Thr123Ile	missense_variant	4/6
FABP6	NM_001130958.2 linkuse as main transcript	c.368C>T	p.Thr123Ile	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP6	ENST00000402432.4 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	2/4	1	NM_001445.3	P1	P51161-1
FABP6	ENST00000393980.8 linkuse as main transcript	c.368C>T	p.Thr123Ile	missense_variant	5/7	1			P51161-2
FABP6	ENST00000521362.1 linkuse as main transcript	n.217C>T		non_coding_transcript_exon_variant	1/3	2
FABP6	ENST00000523955.5 linkuse as main transcript	c.*429C>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1458016

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

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

Feb 23, 2023

The c.368C>T (p.T123I) alteration is located in exon 4 (coding exon 4) of the FABP6 gene. This alteration results from a C to T substitution at nucleotide position 368, causing the threonine (T) at amino acid position 123 to be replaced by an isoleucine (I). 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

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.026

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

1.0

D;D

Vest4

0.69

MutPred

0.61

.;Loss of glycosylation at T74 (P = 0.0196);

MVP

0.53

MPC

0.72

ClinPred

0.99

GERP RS

4.6

Varity_R

0.87

gMVP

0.81

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