Genetic Variant TRPM3:n.252+167484G>A (chr9-71279169-C-T) – 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+167484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,992 control chromosomes in the GnomAD database, including 5,653 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 0.25 ( 5653 hom., cov: 31)

Consequence

TRPM3
ENST00000354500.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Publications

2 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
cataract 50 with or without glaucoma
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

TRPM3 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
TRPM3	NM_001366141.2 link	c.183+167484G>A	intron_variant	Intron 1 of 24	NP_001353070.1
TRPM3	NM_001366142.2 link	c.183+167484G>A	intron_variant	Intron 1 of 26	NP_001353071.1
TRPM3	NM_001366143.2 link	c.183+167484G>A	intron_variant	Intron 1 of 25	NP_001353072.1
TRPM3	NM_001366144.2 link	c.183+167484G>A	intron_variant	Intron 1 of 6	NP_001353073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000354500.6 link	n.252+167484G>A		intron_variant	Intron 1 of 5	1
TRPM3	ENST00000357533.7 link	c.183+167484G>A		intron_variant	Intron 1 of 24	5		ENSP00000350140.2

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37971

AN:

151880

Hom.:

5648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.00635

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.191

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

GnomAD4 genome

AF:

0.250

AC:

38009

AN:

151992

Hom.:

5653

Cov.:

AF XY:

0.246

AC XY:

18304

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.401

AC:

16617

AN:

41410

American (AMR)

AF:

0.151

AC:

2303

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

417

AN:

3470

East Asian (EAS)

AF:

0.00637

AC:

AN:

5184

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4816

European-Finnish (FIN)

AF:

0.245

AC:

2587

AN:

10546

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14862

AN:

67974

Other (OTH)

AF:

0.192

AC:

405

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1250

2500

3750

5000

6250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.208

Hom.:

2857

Bravo

AF:

0.247

Asia WGS

AF:

0.0940

AC:

326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.6

(source)

DANN

Benign

0.69

PhyloP100

0.075

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over