chr9-70810078-T-G

Position:

• chr9-70810078-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001366145.2(TRPM3):​c.973+17769A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00084 in 534,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00087 (1 hom.)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.24

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 9-70810078-T-G is Benign according to our data. Variant chr9-70810078-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1634421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-70810078-T-G is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.973+17769A>C		intron_variant		ENST00000677713.2	NP_001353074.1
MIR204	NR_029621.1	n.7A>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.973+17769A>C		intron_variant			NM_001366145.2	ENSP00000503830	P4
MIR204	ENST00000385200.3	n.7A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.000777 AC: 118 AN: 151952 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000992 AC: 249 AN: 251024 Hom.: 1 AF XY: 0.00104 AC XY: 141 AN XY: 135888

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000865 AC: 331 AN: 382456 Hom.: 1 Cov.: 0 AF XY: 0.000859 AC XY: 187 AN XY: 217720

Gnomad4 AFR exome AF: 0.000381

Gnomad4 AMR exome AF: 0.00278

Gnomad4 ASJ exome AF: 0.000511

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000315

Gnomad4 FIN exome AF: 0.000124

Gnomad4 NFE exome AF: 0.000948

Gnomad4 OTH exome AF: 0.000777

GnomAD4 genome AF: 0.000776 AC: 118 AN: 152070 Hom.: 1 Cov.: 31 AF XY: 0.000861 AC XY: 64 AN XY: 74326

Gnomad4 AFR AF: 0.0000964

Gnomad4 AMR AF: 0.00282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000605 Hom.: 0

Bravo AF: 0.000945

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

TRPM3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 29, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

MIR204-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 29, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs201632779; hg19: chr9-73424994;