ENST00000354500.6:n.252+29421A>C

Variant names:

• chr9-71417232-T-G
• rs12350232
• ENST00000354500.6:n.252+29421A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354500.6(TRPM3):​n.252+29421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,674 control chromosomes in the GnomAD database, including 15,612 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 0.45 (15612 hom., cov: 31)
• Consequence: TRPM3 ENST00000354500.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 7 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366141.2	c.183+29421A>C		intron_variant	Intron 1 of 24		NP_001353070.1
TRPM3	NM_001366142.2	c.183+29421A>C		intron_variant	Intron 1 of 26		NP_001353071.1
TRPM3	NM_001366143.2	c.183+29421A>C		intron_variant	Intron 1 of 25		NP_001353072.1
TRPM3	NM_001366144.2	c.183+29421A>C		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	n.252+29421A>C		intron_variant	Intron 1 of 5	1
TRPM3	ENST00000357533.7	c.183+29421A>C		intron_variant	Intron 1 of 24	5		ENSP00000350140.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68229 AN: 151556 Hom.: 15600 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.450 AC: 68273 AN: 151674 Hom.: 15612 Cov.: 31 AF XY: 0.453 AC XY: 33537 AN XY: 74102

African (AFR) AF: 0.476 AC: 19688 AN: 41402

American (AMR) AF: 0.420 AC: 6392 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1391 AN: 3460

East Asian (EAS) AF: 0.320 AC: 1644 AN: 5136

South Asian (SAS) AF: 0.521 AC: 2503 AN: 4804

European-Finnish (FIN) AF: 0.448 AC: 4735 AN: 10566

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30274 AN: 67796

Other (OTH) AF: 0.438 AC: 922 AN: 2106

Alfa AF: 0.454 Hom.: 9053

Bravo AF: 0.446

Asia WGS AF: 0.446 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12350232; hg19: chr9-74032148;