Variant 6-122781156-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001446.5(FABP7):c.310A>C(p.Asn104His) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FABP7
NM_001446.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21189186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP7	NM_001446.5 link	c.310A>C	p.Asn104His	missense_variant	3/4	ENST00000368444.8	NP_001437.1	O15540-1
FABP7	NM_001319039.2 link	c.310A>C	p.Asn104His	missense_variant	3/3		NP_001305968.1	O15540-2
FABP7	NM_001319042.2 link	c.298A>C	p.Asn100His	missense_variant	3/4		NP_001305971.1	A0A077H155
FABP7	NM_001319041.2 link	c.*645A>C		3_prime_UTR_variant	2/2		NP_001305970.1	Q59HE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000368444.8 link	c.310A>C	p.Asn104His	missense_variant	3/4	1	NM_001446.5	ENSP00000357429.3		O15540-1
FABP7	ENST00000356535.4 link	c.310A>C	p.Asn104His	missense_variant	3/3	1		ENSP00000348931.4		O15540-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

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 19, 2024

The c.310A>C (p.N104H) alteration is located in exon 3 (coding exon 3) of the FABP7 gene. This alteration results from a A to C substitution at nucleotide position 310, causing the asparagine (N) at amino acid position 104 to be replaced by a histidine (H). 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

0.065

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.037

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.099

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0050

D;T

Polyphen

0.0010

B;.

Vest4

0.34

MutPred

0.32

Gain of methylation at K101 (P = 0.0735);Gain of methylation at K101 (P = 0.0735);

MVP

0.29

MPC

0.22

ClinPred

0.69

GERP RS

2.7

Varity_R

0.28

gMVP

0.31

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