rs962001

Positions:

• chr9-71021321-T-C
• chr9-71021321-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.177+99857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,190 control chromosomes in the GnomAD database, including 2,624 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 0.17 (2624 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM3	NM_001366145.2	c.177+99857A>G		intron_variant		ENST00000677713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM3	ENST00000677713.2	c.177+99857A>G		intron_variant			NM_001366145.2	P4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25532 AN: 152072 Hom.: 2621 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0940

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.168 AC: 25531 AN: 152190 Hom.: 2624 Cov.: 32 AF XY: 0.170 AC XY: 12614 AN XY: 74408

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.0940

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.204

Alfa AF: 0.175 Hom.: 397

Bravo AF: 0.159

Asia WGS AF: 0.117 AC: 407 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.65

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: rs962001; hg19: chr9-73636237;