rs7543148
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002023.5(FMOD):c.237G>C(p.Glu79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E79E) has been classified as Benign.
Frequency
Genomes: not found (cov: 31)
Consequence
FMOD
NM_002023.5 missense
NM_002023.5 missense
Scores
3
10
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.576
Genes affected
FMOD (HGNC:3774): (fibromodulin) Fibromodulin belongs to the family of small interstitial proteoglycans. The encoded protein possesses a central region containing leucine-rich repeats with 4 keratan sulfate chains, flanked by terminal domains containing disulphide bonds. Owing to the interaction with type I and type II collagen fibrils and in vitro inhibition of fibrillogenesis, the encoded protein may play a role in the assembly of extracellular matrix. It may also regulate TGF-beta activities by sequestering TGF-beta into the extracellular matrix. Sequence variations in this gene may be associated with the pathogenesis of high myopia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
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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 | UniProt |
---|---|---|---|---|---|---|---|
FMOD | NM_002023.5 | c.237G>C | p.Glu79Asp | missense_variant | 2/3 | ENST00000354955.5 | |
FMOD | XM_047416304.1 | c.237G>C | p.Glu79Asp | missense_variant | 3/4 | ||
FMOD | NR_103757.2 | n.90+2999G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMOD | ENST00000354955.5 | c.237G>C | p.Glu79Asp | missense_variant | 2/3 | 1 | NM_002023.5 | P1 | |
FMOD | ENST00000647586.1 | c.-31G>C | 5_prime_UTR_variant | 2/3 | |||||
FMOD | ENST00000461936.1 | n.54+2999G>C | intron_variant, non_coding_transcript_variant | 3 | |||||
FMOD | ENST00000493296.1 | n.56+2999G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 67
GnomAD4 exome
Cov.:
67
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.0502);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at