9-71121727-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366141.2(TRPM3):​c.184-257216G>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 NM_001366141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.-373G>A		upstream_gene_variant		ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.-373G>A		upstream_gene_variant			NM_001366145.2	ENSP00000503830.2

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

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.432

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

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.474

Alfa AF: 0.424 Hom.: 10263

Bravo AF: 0.424

Asia WGS AF: 0.439 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4620343; hg19: chr9-73736643;