rs112475937
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001032283.3(TMPO):c.991-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,599,648 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001032283.3 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
- dilated cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.991-4T>C | splice_region_variant, intron_variant | Intron 7 of 8 | ENST00000556029.6 | NP_001027454.1 | ||
TMPO | NM_001307975.2 | c.871-4T>C | splice_region_variant, intron_variant | Intron 6 of 7 | NP_001294904.1 | |||
TMPO | NM_001032284.3 | c.664-4T>C | splice_region_variant, intron_variant | Intron 4 of 5 | NP_001027455.1 | |||
TMPO | XM_005269132.5 | c.775-4T>C | splice_region_variant, intron_variant | Intron 5 of 6 | XP_005269189.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0176 AC: 2674AN: 152132Hom.: 74 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00466 AC: 1171AN: 251158 AF XY: 0.00356 show subpopulations
GnomAD4 exome AF: 0.00199 AC: 2880AN: 1447398Hom.: 67 Cov.: 28 AF XY: 0.00177 AC XY: 1273AN XY: 721056 show subpopulations
GnomAD4 genome AF: 0.0176 AC: 2680AN: 152250Hom.: 74 Cov.: 32 AF XY: 0.0172 AC XY: 1281AN XY: 74452 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:2
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not specified Benign:1
c.991-4T>C in Intron 07 of TMPO: This variant is not expected to have clinical s ignificance because it is not located within the splice consensus sequence and h as been identified in 5.4% (201/3738) of African American chromosomes from a bro ad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS; dbSNP rs112475937). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at