9-70746544-G-A

Variant names:

• chr9-70746544-G-A
• rs4744611
• NM_001366145.2:c.1272+15057C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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]

TRPM3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cataract 50 with or without glaucoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cataract-glaucoma syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000303682 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366145.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366145.2	MANE Select	c.1272+15057C>T		intron	N/A	NP_001353074.1
	TRPM3	NM_001366147.2		c.1347+15057C>T		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.1278+15057C>T		intron	N/A	NP_001353070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000677713.2	MANE Select	c.1272+15057C>T		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.1272+15057C>T		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.1272+15057C>T		intron	N/A	ENSP00000366315.4

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

African (AFR) AF: 0.657 AC: 27228 AN: 41432

American (AMR) AF: 0.662 AC: 10101 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2047 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2815 AN: 5166

South Asian (SAS) AF: 0.654 AC: 3146 AN: 4812

European-Finnish (FIN) AF: 0.684 AC: 7218 AN: 10550

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44530 AN: 67964

Other (OTH) AF: 0.644 AC: 1358 AN: 2110

Alfa AF: 0.639 Hom.: 14307

Bravo AF: 0.645

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.50
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: rs4744611; hg19: chr9-73361460;