ENST00000354500.6:n.252+187877A>G

Variant names:

• chr9-71258776-T-C
• rs17056622
• ENST00000354500.6:n.252+187877A>G

Variant summary

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

The ENST00000354500.6(TRPM3):​n.252+187877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,048 control chromosomes in the GnomAD database, including 5,137 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 0.24 (5137 hom., cov: 32)
• Consequence: TRPM3 ENST00000354500.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366141.2	c.183+187877A>G		intron_variant	Intron 1 of 24		NP_001353070.1
TRPM3	NM_001366142.2	c.183+187877A>G		intron_variant	Intron 1 of 26		NP_001353071.1
TRPM3	NM_001366143.2	c.183+187877A>G		intron_variant	Intron 1 of 25		NP_001353072.1
TRPM3	NM_001366144.2	c.183+187877A>G		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+187877A>G		intron_variant	Intron 1 of 5	1
TRPM3	ENST00000357533.7	c.183+187877A>G		intron_variant	Intron 1 of 24	5		ENSP00000350140.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36632 AN: 151930 Hom.: 5132 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.241 AC: 36668 AN: 152048 Hom.: 5137 Cov.: 32 AF XY: 0.238 AC XY: 17689 AN XY: 74344

African (AFR) AF: 0.370 AC: 15326 AN: 41430

American (AMR) AF: 0.150 AC: 2291 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5184

South Asian (SAS) AF: 0.111 AC: 534 AN: 4826

European-Finnish (FIN) AF: 0.246 AC: 2593 AN: 10562

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14823 AN: 67972

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.214 Hom.: 14572

Bravo AF: 0.237

Asia WGS AF: 0.0900 AC: 314 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.061
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: rs17056622; hg19: chr9-73873692;