chr21-14152661-T-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001302998.2(LIPI):c.1030A>C(p.Ile344Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,509,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001302998.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIPI | NM_001302998.2 | c.1030A>C | p.Ile344Leu | missense_variant | 8/10 | ENST00000681601.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIPI | ENST00000681601.1 | c.1030A>C | p.Ile344Leu | missense_variant | 8/10 | NM_001302998.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000202 AC: 50AN: 247042Hom.: 0 AF XY: 0.000194 AC XY: 26AN XY: 133698
GnomAD4 exome AF: 0.000139 AC: 188AN: 1356836Hom.: 0 Cov.: 23 AF XY: 0.000141 AC XY: 96AN XY: 680782
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74430
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | The c.1093A>C (p.I365L) alteration is located in exon 8 (coding exon 8) of the LIPI gene. This alteration results from a A to C substitution at nucleotide position 1093, causing the isoleucine (I) at amino acid position 365 to be replaced by a leucine (L). 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 | Invitae | Jul 25, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with LIPI-related conditions. This variant is present in population databases (rs202154453, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 365 of the LIPI protein (p.Ile365Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at