chr9-70809868-C-T

Variant names:

• chr9-70809868-C-T
• rs7861254
• NM_001366145.2:c.973+17979G>A

Variant summary

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

The NM_001366145.2(TRPM3):​c.973+17979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 483,696 control chromosomes in the GnomAD database, including 18,318 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 0.31 (8507 hom., cov: 31)
  • Exomes 𝑓: 0.24 (9811 hom.)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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: G2P, 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366145.2	MANE Select	c.973+17979G>A		intron	N/A	NP_001353074.1	Q9HCF6-3
	TRPM3	NM_001366147.2		c.1048+1302G>A		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.979+17979G>A		intron	N/A	NP_001353070.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000677713.2	MANE Select	c.973+17979G>A		intron	N/A	ENSP00000503830.2	Q9HCF6-3
	TRPM3	ENST00000377110.9	TSL:1	c.973+17979G>A		intron	N/A	ENSP00000366314.4	Q9HCF6-2
	TRPM3	ENST00000377111.8	TSL:1	c.973+17979G>A		intron	N/A	ENSP00000366315.4	Q9HCF6-10

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46489 AN: 151838 Hom.: 8495 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.235 AC: 77989 AN: 331740 Hom.: 9811 AF XY: 0.235 AC XY: 43633 AN XY: 185922

African (AFR) AF: 0.503 AC: 4670 AN: 9278

American (AMR) AF: 0.201 AC: 6521 AN: 32478

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 2336 AN: 8548

East Asian (EAS) AF: 0.148 AC: 1873 AN: 12642

South Asian (SAS) AF: 0.238 AC: 14014 AN: 58920

European-Finnish (FIN) AF: 0.188 AC: 5314 AN: 28312

Middle Eastern (MID) AF: 0.333 AC: 778 AN: 2334

European-Non Finnish (NFE) AF: 0.236 AC: 38928 AN: 164812

Other (OTH) AF: 0.247 AC: 3555 AN: 14416

GnomAD4 genome AF: 0.306 AC: 46537 AN: 151956 Hom.: 8507 Cov.: 31 AF XY: 0.300 AC XY: 22317 AN XY: 74290

African (AFR) AF: 0.509 AC: 21088 AN: 41404

American (AMR) AF: 0.246 AC: 3764 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3468

East Asian (EAS) AF: 0.135 AC: 698 AN: 5160

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4816

European-Finnish (FIN) AF: 0.189 AC: 2000 AN: 10574

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16023 AN: 67948

Other (OTH) AF: 0.300 AC: 632 AN: 2108

Alfa AF: 0.271 Hom.: 803

Bravo AF: 0.320

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0020
DANN	Benign	0.16
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs7861254; hg19: chr9-73424784; COSMIC: COSV62474544; COSMIC: COSV62474544;