Genetic Variant ENST00000354500.6:n.252+145497A>C (chr9-71301156-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000354500.6(TRPM3):n.252+145497A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,924 control chromosomes in the GnomAD database, including 17,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 17222 hom., cov: 31)

Consequence

TRPM3
ENST00000354500.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.90

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
cataract 50 with or without glaucoma
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cataract-glaucoma syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
schizophrenia
Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TRPM3 links:

LOC107987079 (HGNC:):

LOC107987079 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354500.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
TRPM3	NM_001366141.2	c.183+145497A>C	intron	N/A	NP_001353070.1
TRPM3	NM_001366142.2	c.183+145497A>C	intron	N/A	NP_001353071.1
TRPM3	NM_001366143.2	c.183+145497A>C	intron	N/A	NP_001353072.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000354500.6	TSL:1	n.252+145497A>C		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.183+145497A>C		intron	N/A	ENSP00000350140.2	A2A3F7

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71359

AN:

151806

Hom.:

17215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.470

AC:

71407

AN:

151924

Hom.:

17222

Cov.:

AF XY:

0.469

AC XY:

34833

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.559

AC:

23163

AN:

41424

American (AMR)

AF:

0.436

AC:

6658

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

1737

AN:

3462

East Asian (EAS)

AF:

0.584

AC:

3026

AN:

5178

South Asian (SAS)

AF:

0.507

AC:

2440

AN:

4810

European-Finnish (FIN)

AF:

0.381

AC:

4020

AN:

10556

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28748

AN:

67924

Other (OTH)

AF:

0.479

AC:

1010

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1905

3810

5715

7620

9525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.440

Hom.:

12110

Bravo

AF:

0.477

Asia WGS

AF:

0.540

AC:

1877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0050

(source)

DANN

Benign

0.45

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over