chr9-70536191-A-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001366145.2(TRPM3):c.4922T>G(p.Val1641Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000942 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
TRPM3
NM_001366145.2 missense
NM_001366145.2 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 6.75
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]
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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=0.16663733).
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM3 | NM_001366145.2 | c.4922T>G | p.Val1641Gly | missense_variant | 26/26 | ENST00000677713.2 | |
KLF9-DT | XR_001746707.3 | n.467-14088A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM3 | ENST00000677713.2 | c.4922T>G | p.Val1641Gly | missense_variant | 26/26 | NM_001366145.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251470Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135900
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GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461890Hom.: 0 Cov.: 82 AF XY: 0.0000963 AC XY: 70AN XY: 727244
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74322
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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 06, 2023 | The c.4886T>G (p.V1629G) alteration is located in exon 25 (coding exon 25) of the TRPM3 gene. This alteration results from a T to G substitution at nucleotide position 4886, causing the valine (V) at amino acid position 1629 to be replaced by a glycine (G). 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
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
B;B;B;B;B;.;.;B;B
Vest4
MutPred
0.19
.;.;.;Loss of stability (P = 0.0111);.;.;.;.;.;
MVP
MPC
ClinPred
T
GERP RS
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