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

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000354500.6(TRPM3):​n.253-257216G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: 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: 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>C		intron	N/A	NP_001353070.1
	TRPM3	NM_001366142.2		c.184-257216G>C		intron	N/A	NP_001353071.1
	TRPM3	NM_001366143.2		c.184-257216G>C		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>C		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.184-257216G>C		intron	N/A	ENSP00000350140.2	A2A3F7
	TRPM3	ENST00000677713.2	MANE Select	c.-373G>C		upstream_gene	N/A	ENSP00000503830.2	Q9HCF6-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 538190 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 254362

African (AFR) AF: 0.00 AC: 0 AN: 10860

American (AMR) AF: 0.00 AC: 0 AN: 2138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4652

East Asian (EAS) AF: 0.00 AC: 0 AN: 4622

South Asian (SAS) AF: 0.00 AC: 0 AN: 11558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1222

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 481542

Other (OTH) AF: 0.00 AC: 0 AN: 19068

GnomAD4 genome Cov.: 30

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	9.9
DANN	Benign	0.63
PhyloP100		0.32
PromoterAI		-0.029	Neutral

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;