NM_022840.5:c.950T>C
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022840.5(METTL4):c.950T>C(p.Leu317Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_022840.5 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
METTL4 | ENST00000574538.2 | c.950T>C | p.Leu317Ser | missense_variant | Exon 6 of 9 | 1 | NM_022840.5 | ENSP00000458290.1 | ||
METTL4 | ENST00000573134.1 | n.3251T>C | non_coding_transcript_exon_variant | Exon 4 of 7 | 1 | |||||
METTL4 | ENST00000319888.10 | c.950T>C | p.Leu317Ser | missense_variant | Exon 6 of 8 | 5 | ENSP00000320349.6 | |||
METTL4 | ENST00000576251.5 | c.143T>C | p.Leu48Ser | missense_variant | Exon 3 of 4 | 2 | ENSP00000460774.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000805 AC: 2AN: 248426 AF XY: 0.0000149 show subpopulations
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458932Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4AN XY: 725860 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.950T>C (p.L317S) alteration is located in exon 6 (coding exon 5) of the METTL4 gene. This alteration results from a T to C substitution at nucleotide position 950, causing the leucine (L) at amino acid position 317 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