rs61732970
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_004960.4(FUS):c.404G>A(p.Ser135Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000303 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S135G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004960.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FUS | NM_004960.4 | c.404G>A | p.Ser135Asn | missense_variant | 5/15 | ENST00000254108.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FUS | ENST00000254108.12 | c.404G>A | p.Ser135Asn | missense_variant | 5/15 | 1 | NM_004960.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000611 AC: 93AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000533 AC: 134AN: 251478Hom.: 0 AF XY: 0.000434 AC XY: 59AN XY: 135908
GnomAD4 exome AF: 0.000270 AC: 395AN: 1461870Hom.: 0 Cov.: 36 AF XY: 0.000246 AC XY: 179AN XY: 727234
GnomAD4 genome ? AF: 0.000617 AC: 94AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000671 AC XY: 50AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 12, 2016 | - - |
Amyotrophic lateral sclerosis type 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
FUS-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Amyotrophic lateral sclerosis type 6;C3539195:Tremor, hereditary essential, 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at