chr14-22836890-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004995.4(MMP14):c.73C>T(p.Leu25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,716 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
Consequence
NM_004995.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MMP14 | NM_004995.4 | c.73C>T | p.Leu25Phe | missense_variant | 1/10 | ENST00000311852.11 | NP_004986.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MMP14 | ENST00000311852.11 | c.73C>T | p.Leu25Phe | missense_variant | 1/10 | 1 | NM_004995.4 | ENSP00000308208 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000812 AC: 2AN: 246218Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133942
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461530Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727102
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2023 | The c.73C>T (p.L25F) alteration is located in exon 1 (coding exon 1) of the MMP14 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the leucine (L) at amino acid position 25 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 10, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 25 of the MMP14 protein (p.Leu25Phe). This variant is present in population databases (rs749088113, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MMP14-related conditions. ClinVar contains an entry for this variant (Variation ID: 2528000). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at