rs397516380
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001407322.1(TPM1):c.690-5A>G variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001407322.1 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPM1 | NM_001018005.2 | c.563+254A>G | intron_variant | ENST00000403994.9 | NP_001018005.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TPM1 | ENST00000403994.9 | c.563+254A>G | intron_variant | 1 | NM_001018005.2 | ENSP00000385107.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 genome Cov.: 32
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 | Aug 19, 2011 | Variant classified as Uncertain Significance - Favor Benign. The 564-5A>G varian t has not been reported in the literature but has been detected by our laborato ry in 1 Black individual with DCM. Because the number of Black individuals sequ enced by our laboratory is small, we cannot exclude the possibility that thsi va riant is common in this popualtion. This variant is located in the splice conse nsus sequence but does not affect a highly conserved position. Computer tools d o not predict any effect on mRNA splicing (their accuracy is unknown) and pathog enic splice variants have not yet been reported in the TPM1 gene. In summary, it is very unlikely that this variant is disease causing but additional data is ne eded to confirm this. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at