17-44352062-G-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_002087.4(GRN):c.1227G>T(p.Thr409Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 151,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T409T) has been classified as Benign.
Frequency
Consequence
NM_002087.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRN | ENST00000053867.8 | c.1227G>T | p.Thr409Thr | synonymous_variant | Exon 11 of 13 | 1 | NM_002087.4 | ENSP00000053867.2 | ||
GRN | ENST00000589265.5 | c.756G>T | p.Thr252Thr | synonymous_variant | Exon 7 of 9 | 5 | ENSP00000467616.1 | |||
GRN | ENST00000586443.1 | c.666G>T | p.Thr222Thr | synonymous_variant | Exon 6 of 7 | 3 | ENSP00000465673.1 | |||
GRN | ENST00000586242.1 | c.-142G>T | upstream_gene_variant | 3 | ENSP00000467837.1 |
Frequencies
GnomAD3 genomes AF: 0.0000726 AC: 11AN: 151542Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250936Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135792
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461272Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726976
GnomAD4 genome AF: 0.0000725 AC: 11AN: 151666Hom.: 0 Cov.: 33 AF XY: 0.0000405 AC XY: 3AN XY: 74150
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions;C3539123:Neuronal ceroid lipofuscinosis 11 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at