rs200043160
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_152263.4(TPM3):c.775+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000818 in 1,613,368 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 (★).
Frequency
Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00086 ( 0 hom. )
Consequence
TPM3
NM_152263.4 intron
NM_152263.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.51
Genes affected
TPM3 (HGNC:12012): (tropomyosin 3) This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 1-154170378-A-G is Benign according to our data. Variant chr1-154170378-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 262626.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000433 (66/152256) while in subpopulation NFE AF= 0.000808 (55/68034). AF 95% confidence interval is 0.000638. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM3 | NM_152263.4 | c.775+22T>C | intron_variant | ENST00000651641.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM3 | ENST00000651641.1 | c.775+22T>C | intron_variant | NM_152263.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 65AN: 152138Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
65
AN:
152138
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000565 AC: 142AN: 251330Hom.: 0 AF XY: 0.000618 AC XY: 84AN XY: 135862
GnomAD3 exomes
AF:
AC:
142
AN:
251330
Hom.:
AF XY:
AC XY:
84
AN XY:
135862
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000858 AC: 1254AN: 1461112Hom.: 0 Cov.: 30 AF XY: 0.000919 AC XY: 668AN XY: 726894
GnomAD4 exome
AF:
AC:
1254
AN:
1461112
Hom.:
Cov.:
30
AF XY:
AC XY:
668
AN XY:
726894
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000433 AC: 66AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74462
GnomAD4 genome
?
AF:
AC:
66
AN:
152256
Hom.:
Cov.:
32
AF XY:
AC XY:
27
AN XY:
74462
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at