rs141854925
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024306.5(FA2H):c.1112C>T(p.Thr371Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,560,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024306.5 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FA2H | NM_024306.5 | c.1112C>T | p.Thr371Met | missense_variant | 7/7 | ENST00000219368.8 | NP_077282.3 | |
FA2H | XM_011523319.3 | c.872C>T | p.Thr291Met | missense_variant | 7/7 | XP_011521621.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FA2H | ENST00000219368.8 | c.1112C>T | p.Thr371Met | missense_variant | 7/7 | 1 | NM_024306.5 | ENSP00000219368 | P1 | |
FA2H | ENST00000562145.1 | n.833C>T | non_coding_transcript_exon_variant | 2/2 | 1 | |||||
FA2H | ENST00000567683.5 | c.*391C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 2 | ENSP00000455126 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000286 AC: 49AN: 171506Hom.: 0 AF XY: 0.000352 AC XY: 32AN XY: 90782
GnomAD4 exome AF: 0.000193 AC: 272AN: 1408390Hom.: 0 Cov.: 30 AF XY: 0.000220 AC XY: 153AN XY: 695796
GnomAD4 genome AF: 0.000151 AC: 23AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 16, 2018 | - - |
Hereditary spastic paraplegia 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 18, 2020 | - - |
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 21, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at