14-54478113-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004124.3(GMFB):c.404G>A(p.Arg135His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,455,382 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★).
Frequency
Consequence
NM_004124.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GMFB | ENST00000358056.8 | c.404G>A | p.Arg135His | missense_variant | Exon 7 of 7 | 1 | NM_004124.3 | ENSP00000350757.3 | ||
GMFB | ENST00000553333.1 | c.443G>A | p.Arg148His | missense_variant | Exon 8 of 8 | 3 | ENSP00000451920.1 | |||
GMFB | ENST00000554908.5 | c.*2877G>A | 3_prime_UTR_variant | Exon 4 of 4 | 1 | ENSP00000452410.1 |
Frequencies
GnomAD3 genomes AF: 0.0000265 AC: 4AN: 150896Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000122 AC: 22AN: 180412Hom.: 0 AF XY: 0.000162 AC XY: 16AN XY: 98640
GnomAD4 exome AF: 0.0000621 AC: 81AN: 1304374Hom.: 2 Cov.: 19 AF XY: 0.0000893 AC XY: 58AN XY: 649520
GnomAD4 genome AF: 0.0000265 AC: 4AN: 151008Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2AN XY: 73664
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.404G>A (p.R135H) alteration is located in exon 7 (coding exon 7) of the GMFB gene. This alteration results from a G to A substitution at nucleotide position 404, causing the arginine (R) at amino acid position 135 to be replaced by a histidine (H). 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