3-133380067-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_023943.4(TMEM108):c.356C>T(p.Pro119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,888 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_023943.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM108 | NM_023943.4 | c.356C>T | p.Pro119Leu | missense_variant | Exon 4 of 6 | ENST00000321871.11 | NP_076432.1 | |
TMEM108 | NM_001136469.3 | c.356C>T | p.Pro119Leu | missense_variant | Exon 4 of 6 | NP_001129941.1 | ||
TMEM108 | NM_001282865.2 | c.41-10113C>T | intron_variant | Intron 2 of 3 | NP_001269794.1 | |||
LOC101927432 | NR_189054.1 | n.131+1596G>A | intron_variant | Intron 1 of 6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152080Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249754Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135382
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461808Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727210
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74272
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.356C>T (p.P119L) alteration is located in exon 4 (coding exon 2) of the TMEM108 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the proline (P) at amino acid position 119 to be replaced by a leucine (L). 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