chr4-143611320-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001168235.2(FREM3):c.5987T>A(p.Phe1996Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000578 in 1,384,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000058 ( 0 hom. )
Consequence
FREM3
NM_001168235.2 missense
NM_001168235.2 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.53
Genes affected
FREM3 (HGNC:25172): (FRAS1 related extracellular matrix 3) This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The protein belongs to the family of FRAS1/FREM extracellular matrix proteins and may play a role cell adhesion. [provided by RefSeq, Feb 2017]
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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=0.19549057).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FREM3 | NM_001168235.2 | c.5987T>A | p.Phe1996Tyr | missense_variant | 6/8 | ENST00000329798.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FREM3 | ENST00000329798.5 | c.5987T>A | p.Phe1996Tyr | missense_variant | 6/8 | 5 | NM_001168235.2 | P1 | |
GUSBP5 | ENST00000641328.1 | n.861+38739A>T | intron_variant, non_coding_transcript_variant | ||||||
FREM3 | ENST00000508899.1 | n.224T>A | non_coding_transcript_exon_variant | 2/3 | 5 | ||||
GUSBP5 | ENST00000511042.5 | n.192-33765A>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000141 AC: 2AN: 141794Hom.: 0 AF XY: 0.0000264 AC XY: 2AN XY: 75894
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GnomAD4 exome AF: 0.00000578 AC: 8AN: 1384764Hom.: 0 Cov.: 31 AF XY: 0.00000585 AC XY: 4AN XY: 683312
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GnomAD4 genome ? Cov.: 33
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Cov.:
33
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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 | Jun 06, 2023 | The c.5987T>A (p.F1996Y) alteration is located in exon 6 (coding exon 6) of the FREM3 gene. This alteration results from a T to A substitution at nucleotide position 5987, causing the phenylalanine (F) at amino acid position 1996 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Gain of catalytic residue at F1996 (P = 0.0178);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at