chr19-16081925-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_003290.3(TPM4):c.145G>A(p.Val49Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,598,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
TPM4
NM_003290.3 missense
NM_003290.3 missense
Scores
7
8
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.83
Genes affected
TPM4 (HGNC:12013): (tropomyosin 4) This gene encodes a member of the tropomyosin family of actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosins are dimers of coiled-coil proteins that polymerize end-to-end along the major groove in most actin filaments. They provide stability to the filaments and regulate access of other actin-binding proteins. In muscle cells, they regulate muscle contraction by controlling the binding of myosin heads to the actin filament. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM4 | NM_003290.3 | c.145G>A | p.Val49Met | missense_variant | 2/8 | ENST00000643579.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM4 | ENST00000643579.2 | c.145G>A | p.Val49Met | missense_variant | 2/8 | NM_003290.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000679 AC: 17AN: 250508Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135508
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GnomAD4 exome AF: 0.0000138 AC: 20AN: 1445882Hom.: 0 Cov.: 30 AF XY: 0.0000112 AC XY: 8AN XY: 716430
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74338
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;.;.;N;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.;D;.;.;.
Sift4G
Uncertain
T;.;D;D;D;.;D;.
Polyphen
D;D;.;.;D;D;.;.
Vest4
MutPred
0.71
.;.;.;.;Gain of MoRF binding (P = 0.1175);Gain of MoRF binding (P = 0.1175);.;.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at