rs375272740
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002458.3(MUC5B):āc.16960G>Cā(p.Glu5654Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,612,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_002458.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MUC5B | NM_002458.3 | c.16960G>C | p.Glu5654Gln | missense_variant | 47/49 | ENST00000529681.5 | NP_002449.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUC5B | ENST00000529681.5 | c.16960G>C | p.Glu5654Gln | missense_variant | 47/49 | 5 | NM_002458.3 | ENSP00000436812 | P1 | |
MUC5B | ENST00000526859.1 | c.435+545G>C | intron_variant | 3 | ENSP00000434539 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 246726Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134702
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1460246Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 726398
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 10, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Glu5654Gln va riant in MUC5B has not been previously reported in individuals with cardiomyopat hy, but has been identified in 4/63298 European chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs375272740). Gluta mic acid (Glu) at position 5654 is not conserved in mammals or evolutionarily di stant species and 2 mammals (hedgehog and wallaby) carry a glutamine (Gln) at th is position, raising the possibility that this change may be tolerated. Addition al computational prediction tools support that the p.Glu5654Gln variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Glu5654Gln variant is uncertain, these data suggest that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at