chr2-207861117-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001080475.3(PLEKHM3):āc.2096T>Cā(p.Ile699Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,984 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I699M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001080475.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM3 | NM_001080475.3 | c.2096T>C | p.Ile699Thr | missense_variant | 7/8 | ENST00000427836.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM3 | ENST00000427836.8 | c.2096T>C | p.Ile699Thr | missense_variant | 7/8 | 5 | NM_001080475.3 | P1 | |
PLEKHM3 | ENST00000447645.5 | c.1352T>C | p.Ile451Thr | missense_variant | 5/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460782Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726628
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.2096T>C (p.I699T) alteration is located in exon 7 (coding exon 6) of the PLEKHM3 gene. This alteration results from a T to C substitution at nucleotide position 2096, causing the isoleucine (I) at amino acid position 699 to be replaced by a threonine (T). 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