chr6-122781156-A-C

Variant summary

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

The NM_001446.5(FABP7):ā€‹c.310A>Cā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

FABP7
NM_001446.5 missense

Scores

4
15

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]

Genome browser will be placed here

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
FABP7NM_001446.5 linkc.310A>C p.Asn104His missense_variant 3/4 ENST00000368444.8 NP_001437.1 O15540-1
FABP7NM_001319039.2 linkc.310A>C p.Asn104His missense_variant 3/3 NP_001305968.1 O15540-2
FABP7NM_001319042.2 linkc.298A>C p.Asn100His missense_variant 3/4 NP_001305971.1 A0A077H155
FABP7NM_001319041.2 linkc.*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
FABP7ENST00000368444.8 linkc.310A>C p.Asn104His missense_variant 3/41 NM_001446.5 ENSP00000357429.3 O15540-1
FABP7ENST00000356535.4 linkc.310A>C p.Asn104His missense_variant 3/31 ENSP00000348931.4 O15540-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152174
Hom.:
0
Cov.:
33
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:
1
AN:
1461726
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
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:
2
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
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 submitterclinical testingAmbry GeneticsNov 19, 2024The 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
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;.
Eigen
Benign
-0.037
Eigen_PC
Benign
0.032
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.85
T;T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.27
T
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
D
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.

Other links and lift over

dbSNP: rs963939342; hg19: chr6-123102301; API