Variant 6-122780423-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000368444.8(FABP7):c.206A>G(p.Glu69Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E69K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FABP7
ENST00000368444.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Variant links:

Genes affected

FABP7 (HGNC:3562): (fatty acid binding protein 7) The gene encodes a small, highly conserved cytoplasmic protein that bind long-chain fatty acids and other hydrophobic ligands. The encoded protein is important in the establishment of the radial glial fiber in the developing brain. Alternative splicing and promoter usage results in multiple transcript variants encoding different isoforms. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Jan 2016]

FABP7 links:

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ACMG classification

Classification made for transcript

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, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FABP7	NM_001446.5 linkuse as main transcript	c.206A>G	p.Glu69Gly	missense_variant	2/4	ENST00000368444.8	NP_001437.1
FABP7	NM_001319039.2 linkuse as main transcript	c.206A>G	p.Glu69Gly	missense_variant	2/3		NP_001305968.1
FABP7	NM_001319042.2 linkuse as main transcript	c.194A>G	p.Glu65Gly	missense_variant	2/4		NP_001305971.1
FABP7	NM_001319041.2 linkuse as main transcript	c.206A>G	p.Glu69Gly	missense_variant	2/2		NP_001305970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000368444.8 linkuse as main transcript	c.206A>G	p.Glu69Gly	missense_variant	2/4	1	NM_001446.5	ENSP00000357429	P1	O15540-1
FABP7	ENST00000356535.4 linkuse as main transcript	c.206A>G	p.Glu69Gly	missense_variant	2/3	1		ENSP00000348931		O15540-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250878

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135574

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:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461616

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 21, 2022

The c.206A>G (p.E69G) alteration is located in exon 2 (coding exon 2) of the FABP7 gene. This alteration results from a A to G substitution at nucleotide position 206, causing the glutamic acid (E) at amino acid position 69 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.073

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.97

D;.

Vest4

0.70

MutPred

0.61

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.76

MPC

0.74

ClinPred

0.97

GERP RS

3.1

Varity_R

0.90

gMVP

0.80

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