Genetic Variant NM_001366145.2:c.5045G>A (chr9-70536068-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366145.2(TRPM3):c.5045G>A(p.Arg1682Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,613,982 control chromosomes in the GnomAD database, including 261,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26643 hom., cov: 32)

Exomes 𝑓: 0.56 ( 235232 hom. )

Consequence

TRPM3
NM_001366145.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.57

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]

TRPM3 links:

KLF9-DT (HGNC:54815): (KLF9 divergent transcript)

KLF9-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2846781E-6).

BP6

Variant 9-70536068-C-T is Benign according to our data. Variant chr9-70536068-C-T is described in ClinVar as [Benign]. Clinvar id is 1232067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2 link	c.5045G>A	p.Arg1682Gln	missense_variant	Exon 26 of 26	ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2 link	c.5045G>A	p.Arg1682Gln	missense_variant	Exon 26 of 26		NM_001366145.2	ENSP00000503830.2		Q9HCF6-3A0A7I2V4E8

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89386

AN:

151986

Hom.:

26625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.653

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.584

GnomAD3 exomes

AF:

0.580

AC:

145754

AN:

251452

Hom.:

43461

AF XY:

0.569

AC XY:

77325

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.632

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.841

Gnomad SAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.655

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.564

AC:

824096

AN:

1461878

Hom.:

235232

Cov.:

AF XY:

0.559

AC XY:

406702

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.565

Gnomad4 ASJ exome

AF:

0.569

Gnomad4 EAS exome

AF:

0.798

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.656

Gnomad4 NFE exome

AF:

0.560

Gnomad4 OTH exome

AF:

0.566

GnomAD4 genome

AF:

0.588

AC:

89440

AN:

152104

Hom.:

26643

Cov.:

AF XY:

0.590

AC XY:

43868

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.630

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.573

Gnomad4 EAS

AF:

0.821

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.653

Gnomad4 NFE

AF:

0.557

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.572

Hom.:

47564

Bravo

AF:

0.593

TwinsUK

AF:

0.561

AC:

2082

ALSPAC

AF:

0.565

AC:

2177

ESP6500AA

AF:

0.621

AC:

2735

ESP6500EA

AF:

0.551

AC:

4741

ExAC

AF:

0.579

AC:

70238

Asia WGS

AF:

0.580

AC:

2017

AN:

3478

EpiCase

AF:

0.565

EpiControl

AF:

0.568

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 25, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

.;.;T;T;T;.;.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D;.;.

MetaRNN

Benign

0.0000013

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.88

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.045

D;T;T;T;T;T;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;D;D;P;D;.;.;D;D

Vest4

0.46

MPC

0.58

ClinPred

0.020

GERP RS

5.8

gMVP

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over