9-70550347-T-C

Variant names:

• chr9-70550347-T-C
• rs7025694
• NM_001366145.2:c.3575-673A>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.3575-673A>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 152,084 control chromosomes in the GnomAD database, including 18,659 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 (18659 hom., cov: 33)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.3575-673A>G		intron_variant	Intron 24 of 25	ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.3575-673A>G		intron_variant	Intron 24 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74125 AN: 151966 Hom.: 18656 Cov.: 33

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.606

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: 74153 AN: 152084 Hom.: 18659 Cov.: 33 AF XY: 0.490 AC XY: 36416 AN XY: 74336

African (AFR) AF: 0.406 AC: 16824 AN: 41486

American (AMR) AF: 0.494 AC: 7538 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1814 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4240 AN: 5168

South Asian (SAS) AF: 0.341 AC: 1647 AN: 4824

European-Finnish (FIN) AF: 0.606 AC: 6402 AN: 10568

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

European-Non Finnish (NFE) AF: 0.501 AC: 34073 AN: 67980

Other (OTH) AF: 0.491 AC: 1036 AN: 2110

Alfa AF: 0.489 Hom.: 2280

Bravo AF: 0.486

Asia WGS AF: 0.524 AC: 1823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.40
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: rs7025694; hg19: chr9-73165263;