9-70548684-T-C

Variant names:

• chr9-70548684-T-C
• rs10780946
• NM_001366145.2:c.3707+858A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366145.2(TRPM3):​c.3707+858A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,178 control chromosomes in the GnomAD database, including 18,674 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 (18674 hom., cov: 34)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 4 publications found

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]

ENSG00000308298 (HGNC:):

KLF9-DT (HGNC:54815): (KLF9 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.3707+858A>G		intron_variant	Intron 25 of 25	ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.3707+858A>G		intron_variant	Intron 25 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74181 AN: 152060 Hom.: 18671 Cov.: 34

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.488 AC: 74208 AN: 152178 Hom.: 18674 Cov.: 34 AF XY: 0.490 AC XY: 36457 AN XY: 74396

African (AFR) AF: 0.405 AC: 16827 AN: 41506

American (AMR) AF: 0.494 AC: 7551 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4241 AN: 5190

South Asian (SAS) AF: 0.342 AC: 1650 AN: 4830

European-Finnish (FIN) AF: 0.607 AC: 6418 AN: 10582

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34088 AN: 67984

Other (OTH) AF: 0.491 AC: 1040 AN: 2116

Alfa AF: 0.485 Hom.: 2341

Bravo AF: 0.486

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Benign	0.40
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10780946; hg19: chr9-73163600;