Genetic Variant TRPM3:n.253-257216G>T (chr9-71121727-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366141.2(TRPM3):c.184-257216G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRPM3
NM_001366141.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.324

Publications

6 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366141.2. 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.184-257216G>T	intron	N/A	NP_001353070.1
TRPM3	NM_001366142.2	c.184-257216G>T	intron	N/A	NP_001353071.1
TRPM3	NM_001366143.2	c.184-257216G>T	intron	N/A	NP_001353072.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPM3	ENST00000354500.6	TSL:1	n.253-257216G>T	intron	N/A
TRPM3	ENST00000357533.7	TSL:5	c.184-257216G>T	intron	N/A	ENSP00000350140.2	A2A3F7
TRPM3	ENST00000677713.2	MANE Select	c.-373G>T	upstream_gene	N/A	ENSP00000503830.2	Q9HCF6-3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

538188

Hom.:

AF XY:

0.00

AC XY:

AN XY:

254362

African (AFR)

AF:

0.00

AC:

AN:

10860

American (AMR)

AF:

0.00

AC:

AN:

2138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4652

East Asian (EAS)

AF:

0.00

AC:

AN:

4622

South Asian (SAS)

AF:

0.00

AC:

AN:

11558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

481540

Other (OTH)

AF:

0.00

AC:

AN:

19068

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73938

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41162

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

14275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.8

(source)

DANN

Benign

0.74

PhyloP100

0.32

PromoterAI

-0.028

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over