chr19-16093694-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_003290.3(TPM4):c.605G>A(p.Arg202His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
TPM4
NM_003290.3 missense
NM_003290.3 missense
Scores
12
3
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.83
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.901
BS2
High AC in GnomAdExome4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM4 | NM_003290.3 | c.605G>A | p.Arg202His | missense_variant | 7/8 | ENST00000643579.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM4 | ENST00000643579.2 | c.605G>A | p.Arg202His | missense_variant | 7/8 | NM_003290.3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
31
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: 0.0000119 AC: 3AN: 251480Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135912
GnomAD3 exomes
AF:
AC:
3
AN:
251480
Hom.:
AF XY:
AC XY:
3
AN XY:
135912
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: 0.0000164 AC: 24AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727240
GnomAD4 exome
AF:
AC:
24
AN:
1461874
Hom.:
Cov.:
32
AF XY:
AC XY:
12
AN XY:
727240
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: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74334
GnomAD4 genome
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74334
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:
EpiCase
AF:
EpiControl
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;.;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;D;.;.
Sift4G
Pathogenic
D;.;.;D;.;.
Polyphen
D;D;.;P;P;.
Vest4
MutPred
0.75
.;.;.;Loss of methylation at R202 (P = 0.0339);Loss of methylation at R202 (P = 0.0339);.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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