9-70746544-G-A

Position:

• chr9-70746544-G-A

Variant summary

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

The NM_001366145.2(TRPM3):​c.1272+15057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,960 control chromosomes in the GnomAD database, including 32,452 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 0.65 (32452 hom., cov: 31)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM3	NM_001366145.2	c.1272+15057C>T		intron_variant		ENST00000677713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM3	ENST00000677713.2	c.1272+15057C>T		intron_variant			NM_001366145.2	P4

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99056 AN: 151842 Hom.: 32433 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99118 AN: 151960 Hom.: 32452 Cov.: 31 AF XY: 0.654 AC XY: 48580 AN XY: 74268

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.644

Alfa AF: 0.635 Hom.: 11653

Bravo AF: 0.645

Asia WGS AF: 0.626 AC: 2177 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	1.0
DANN	Benign	0.59

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: rs4744611; hg19: chr9-73361460;