9-70810048-G-C

Variant names:

• chr9-70810048-G-C
• rs767146880
• NM_001366145.2:c.973+17799C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366145.2(TRPM3):​c.973+17799C>G variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 382,462 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.94
• Publications: 5 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]

MIR204 (HGNC:31582): (microRNA 204) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR204 Gene-Disease associations (from GenCC):

• familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366145.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366145.2	MANE Select	c.973+17799C>G		intron	N/A	NP_001353074.1
	MIR204	NR_029621.1		n.37C>G		non_coding_transcript_exon	Exon 1 of 1
	TRPM3	NM_001366147.2		c.1048+1122C>G		intron	N/A	NP_001353076.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000677713.2	MANE Select	c.973+17799C>G		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.973+17799C>G		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.973+17799C>G		intron	N/A	ENSP00000366315.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251036 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000261 AC: 1 AN: 382462 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 217730

African (AFR) AF: 0.00 AC: 0 AN: 10514

American (AMR) AF: 0.00 AC: 0 AN: 36306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11742

East Asian (EAS) AF: 0.00 AC: 0 AN: 13176

South Asian (SAS) AF: 0.00 AC: 0 AN: 66764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2854

European-Non Finnish (NFE) AF: 0.00000521 AC: 1 AN: 192062

Other (OTH) AF: 0.00 AC: 0 AN: 16726

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.88
PhyloP100		8.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs767146880; hg19: chr9-73424964;