5-160232210-G-C

Position:

chr5-160232210-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000402432.4(FABP6):c.180G>C(p.Met60Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,190 control chromosomes in the GnomAD database, including 3 homozygotes. 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: 𝑓 0.00076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

FABP6
ENST00000402432.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.168

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015870541).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FABP6	NM_001445.3 linkuse as main transcript	c.180G>C	p.Met60Ile	missense_variant	2/4	ENST00000402432.4	NP_001436.1
FABP6	NM_001040442.1 linkuse as main transcript	c.327G>C	p.Met109Ile	missense_variant	4/6		NP_001035532.1
FABP6	NM_001130958.2 linkuse as main transcript	c.327G>C	p.Met109Ile	missense_variant	5/7		NP_001124430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP6	ENST00000402432.4 linkuse as main transcript	c.180G>C	p.Met60Ile	missense_variant	2/4	1	NM_001445.3	ENSP00000385433	P1	P51161-1
FABP6	ENST00000393980.8 linkuse as main transcript	c.327G>C	p.Met109Ile	missense_variant	5/7	1		ENSP00000377549		P51161-2
FABP6	ENST00000521362.1 linkuse as main transcript	n.176G>C		non_coding_transcript_exon_variant	1/3	2
FABP6	ENST00000523955.5 linkuse as main transcript	c.*388G>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	3		ENSP00000428766

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000581

AC:

145

AN:

249360

Hom.:

AF XY:

0.000512

AC XY:

AN XY:

134798

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000822

GnomAD4 exome

AF:

0.00106

AC:

1549

AN:

1461050

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

730

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152140

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000616

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.000536

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

Oct 06, 2021

The c.327G>C (p.M109I) alteration is located in exon 4 (coding exon 4) of the FABP6 gene. This alteration results from a G to C substitution at nucleotide position 327, causing the methionine (M) at amino acid position 109 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

Benign

0.21

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.6

DANN

Benign

0.90

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.080

.;N

MutationTaster

Benign

0.86

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.028

Sift

Benign

0.47

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0020

B;B

Vest4

0.14

MutPred

0.32

.;Loss of ubiquitination at K63 (P = 0.0615);

MVP

0.061

MPC

0.19

ClinPred

0.0037

GERP RS

0.15

Varity_R

0.25

gMVP

0.24

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