ENST00000354500.6:n.253-257216G>A

Variant names:

• chr9-71121727-C-T
• rs4620343
• ENST00000354500.6:n.253-257216G>A

Variant summary

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

The ENST00000354500.6(TRPM3):​n.253-257216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 687,760 control chromosomes in the GnomAD database, including 64,806 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 0.43 (14173 hom., cov: 30)
  • Exomes 𝑓: 0.43 (50633 hom.)
• Consequence: TRPM3 ENST00000354500.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 6 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: 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366141.2		c.184-257216G>A		intron	N/A	NP_001353070.1
	TRPM3	NM_001366142.2		c.184-257216G>A		intron	N/A	NP_001353071.1
	TRPM3	NM_001366143.2		c.184-257216G>A		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.253-257216G>A		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.184-257216G>A		intron	N/A	ENSP00000350140.2	A2A3F7
	TRPM3	ENST00000677713.2	MANE Select	c.-373G>A		upstream_gene	N/A	ENSP00000503830.2	Q9HCF6-3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65113 AN: 151374 Hom.: 14165 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.432 AC: 231638 AN: 536270 Hom.: 50633 AF XY: 0.431 AC XY: 109264 AN XY: 253442

African (AFR) AF: 0.405 AC: 4383 AN: 10810

American (AMR) AF: 0.397 AC: 845 AN: 2130

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 2477 AN: 4636

East Asian (EAS) AF: 0.430 AC: 1975 AN: 4598

South Asian (SAS) AF: 0.474 AC: 5451 AN: 11508

European-Finnish (FIN) AF: 0.398 AC: 1003 AN: 2520

Middle Eastern (MID) AF: 0.537 AC: 654 AN: 1218

European-Non Finnish (NFE) AF: 0.431 AC: 206657 AN: 479878

Other (OTH) AF: 0.432 AC: 8193 AN: 18972

GnomAD4 genome AF: 0.430 AC: 65136 AN: 151490 Hom.: 14173 Cov.: 30 AF XY: 0.431 AC XY: 31869 AN XY: 73982

African (AFR) AF: 0.396 AC: 16327 AN: 41226

American (AMR) AF: 0.413 AC: 6283 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2146 AN: 5110

South Asian (SAS) AF: 0.462 AC: 2209 AN: 4782

European-Finnish (FIN) AF: 0.443 AC: 4642 AN: 10482

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30066 AN: 67888

Other (OTH) AF: 0.474 AC: 997 AN: 2102

Alfa AF: 0.429 Hom.: 14275

Bravo AF: 0.424

Asia WGS AF: 0.439 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.32
PromoterAI		0.14	Neutral
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: rs4620343; hg19: chr9-73736643;