chr16-715699-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024042.4(METRN):c.220C>T(p.Pro74Ser) 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 1,394,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024042.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
METRN | ENST00000568223.7 | c.220C>T | p.Pro74Ser | missense_variant | Exon 2 of 4 | 1 | NM_024042.4 | ENSP00000455068.1 | ||
METRN | ENST00000219542.3 | c.172C>T | p.Pro58Ser | missense_variant | Exon 2 of 3 | 2 | ENSP00000219542.3 | |||
METRN | ENST00000567076.5 | c.58C>T | p.Pro20Ser | missense_variant | Exon 1 of 4 | 5 | ENSP00000459900.1 | |||
METRN | ENST00000570132.1 | n.105-177C>T | intron_variant | Intron 1 of 3 | 3 | ENSP00000456647.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 151950Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000786 AC: 3AN: 38152Hom.: 0 AF XY: 0.0000426 AC XY: 1AN XY: 23494
GnomAD4 exome AF: 0.00000885 AC: 11AN: 1242958Hom.: 0 Cov.: 31 AF XY: 0.00000818 AC XY: 5AN XY: 611072
GnomAD4 genome AF: 0.0000526 AC: 8AN: 151950Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74228
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.220C>T (p.P74S) alteration is located in exon 2 (coding exon 2) of the METRN gene. This alteration results from a C to T substitution at nucleotide position 220, causing the proline (P) at amino acid position 74 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at