9-70536143-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001366145.2(TRPM3):​c.4970C>T​(p.Ala1657Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,614,206 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

TRPM3
NM_001366145.2 missense

Scores

17

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.527
Variant links:
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]
KLF9-DT (HGNC:54815): (KLF9 divergent transcript)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004575461).
BP6
Variant 9-70536143-G-A is Benign according to our data. Variant chr9-70536143-G-A is described in ClinVar as [Benign]. Clinvar id is 2659246.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRPM3NM_001366145.2 linkc.4970C>T p.Ala1657Val missense_variant Exon 26 of 26 ENST00000677713.2 NP_001353074.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRPM3ENST00000677713.2 linkc.4970C>T p.Ala1657Val missense_variant Exon 26 of 26 NM_001366145.2 ENSP00000503830.2 Q9HCF6-3A0A7I2V4E8

Frequencies

GnomAD3 genomes
AF:
0.00116
AC:
177
AN:
152202
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00203
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000994
AC:
250
AN:
251420
Hom.:
2
AF XY:
0.000971
AC XY:
132
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.000893
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000323
Gnomad NFE exome
AF:
0.00179
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00143
AC:
2089
AN:
1461886
Hom.:
2
Cov.:
81
AF XY:
0.00133
AC XY:
966
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.000612
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.000281
Gnomad4 NFE exome
AF:
0.00175
Gnomad4 OTH exome
AF:
0.00113
GnomAD4 genome
AF:
0.00116
AC:
177
AN:
152320
Hom.:
1
Cov.:
32
AF XY:
0.00103
AC XY:
77
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00203
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00153
Hom.:
0
Bravo
AF:
0.00109
TwinsUK
AF:
0.00297
AC:
11
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00151
AC:
13
ExAC
AF:
0.000947
AC:
115
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00120
EpiControl
AF:
0.00196

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TRPM3-related disorder Benign:1
Feb 01, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
May 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

TRPM3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.73
DANN
Benign
0.30
DEOGEN2
Benign
0.064
.;.;T;T;T;.;.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.82
T;T;T;T;T;T;T;.;.
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.0046
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.56
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.082
Sift
Benign
0.51
T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.25
T;T;T;T;T;T;T;T;T
Polyphen
0.0
B;B;B;B;B;.;.;B;B
Vest4
0.019
MVP
0.15
MPC
0.11
ClinPred
0.0041
T
GERP RS
0.63
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148848073; hg19: chr9-73151059; COSMIC: COSV62584188; API