rs1889915

Positions:

• chr9-70549796-T-C
• chr9-70549796-T-G

Variant summary

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

The NM_001366145.2(TRPM3):​c.3575-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 989,682 control chromosomes in the GnomAD database, including 120,942 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 0.49 (18741 hom., cov: 31)
  • Exomes 𝑓: 0.48 (102201 hom.)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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]

KLF9-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.3575-122A>G		intron_variant		ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.3575-122A>G		intron_variant			NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74295 AN: 151872 Hom.: 18740 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.485 AC: 405998 AN: 837692 Hom.: 102201 AF XY: 0.481 AC XY: 201382 AN XY: 418534

Gnomad4 AFR exome AF: 0.398

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.787

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.489 AC: 74323 AN: 151990 Hom.: 18741 Cov.: 31 AF XY: 0.492 AC XY: 36508 AN XY: 74260

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.493

Alfa AF: 0.506 Hom.: 40076

Bravo AF: 0.488

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.64

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: rs1889915; hg19: chr9-73164712;