chr9-70678150-A-G

Variant names:

• chr9-70678150-A-G
• rs1317604
• NM_001366145.2:c.1345+3356T>C

Variant summary

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

The NM_001366145.2(TRPM3):​c.1345+3356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,042 control chromosomes in the GnomAD database, including 33,172 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 0.66 (33172 hom., cov: 31)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• 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]

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)

LOC105376078 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 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.1345+3356T>C		intron	N/A	NP_001353074.1
	TRPM3	NM_001366147.2		c.1420+3356T>C		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.1351+3356T>C		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.1345+3356T>C		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.1345+3356T>C		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.1345+3356T>C		intron	N/A	ENSP00000366315.4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99696 AN: 151924 Hom.: 33139 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.656 AC: 99781 AN: 152042 Hom.: 33172 Cov.: 31 AF XY: 0.657 AC XY: 48817 AN XY: 74294

African (AFR) AF: 0.759 AC: 31506 AN: 41492

American (AMR) AF: 0.562 AC: 8578 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2101 AN: 3470

East Asian (EAS) AF: 0.647 AC: 3340 AN: 5164

South Asian (SAS) AF: 0.722 AC: 3476 AN: 4814

European-Finnish (FIN) AF: 0.647 AC: 6836 AN: 10562

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41809 AN: 67956

Other (OTH) AF: 0.637 AC: 1343 AN: 2108

Alfa AF: 0.647 Hom.: 4675

Bravo AF: 0.651

Asia WGS AF: 0.691 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.23
PhyloP100		-0.050
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: rs1317604; hg19: chr9-73293066;