chr9-70536569-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001366145.2(TRPM3):c.4544G>A(p.Arg1515His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,038 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
TRPM3
NM_001366145.2 missense
NM_001366145.2 missense
Scores
5
6
5
Clinical Significance
Conservation
PhyloP100: 7.38
Genes affected
TRPM3 (HGNC:17992): (transient receptor potential cation channel subfamily M member 3) The product of this gene belongs to the family of transient receptor potential (TRP) channels. TRP channels are cation-selective channels important for cellular calcium signaling and homeostasis. The protein encoded by this gene mediates calcium entry, and this entry is potentiated by calcium store depletion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRPM3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19587803).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM3 | NM_001366145.2 | c.4544G>A | p.Arg1515His | missense_variant | 26/26 | ENST00000677713.2 | |
KLF9-DT | XR_001746707.3 | n.467-13710C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM3 | ENST00000677713.2 | c.4544G>A | p.Arg1515His | missense_variant | 26/26 | NM_001366145.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152074Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
152074
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: 0.0000915 AC: 23AN: 251302Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135838
GnomAD3 exomes
AF:
AC:
23
AN:
251302
Hom.:
AF XY:
AC XY:
14
AN XY:
135838
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: 0.0000328 AC: 48AN: 1461846Hom.: 0 Cov.: 82 AF XY: 0.0000385 AC XY: 28AN XY: 727226
GnomAD4 exome
AF:
AC:
48
AN:
1461846
Hom.:
Cov.:
82
AF XY:
AC XY:
28
AN XY:
727226
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: 0.0000394 AC: 6AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74412
GnomAD4 genome
?
AF:
AC:
6
AN:
152192
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74412
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
13
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 28, 2023 | The c.4508G>A (p.R1503H) alteration is located in exon 25 (coding exon 25) of the TRPM3 gene. This alteration results from a G to A substitution at nucleotide position 4508, causing the arginine (R) at amino acid position 1503 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;.;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;D;.;.;D;D
Vest4
MutPred
0.51
.;.;.;Gain of ubiquitination at K1504 (P = 0.0312);.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
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