rs962001

Variant names:

• chr9-71021321-T-C
• rs962001
• NM_001366145.2:c.177+99857A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-71021321-T-C
• chr9-71021321-T-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.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
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• cataract 50 with or without glaucoma

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

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 (NFE) allele frequency at 95% confidence interval = 0.215 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366145.2	MANE Select	c.177+99857A>G		intron	N/A	NP_001353074.1	Q9HCF6-3
	TRPM3	NM_001366147.2		c.177+99857A>G		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.184-156810A>G		intron	N/A	NP_001353070.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000677713.2	MANE Select	c.177+99857A>G		intron	N/A	ENSP00000503830.2	Q9HCF6-3
	TRPM3	ENST00000377110.9	TSL:1	c.177+99857A>G		intron	N/A	ENSP00000366314.4	Q9HCF6-2
	TRPM3	ENST00000377111.8	TSL:1	c.177+99857A>G		intron	N/A	ENSP00000366315.4	Q9HCF6-10

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

African (AFR) AF: 0.0530 AC: 2201 AN: 41558

American (AMR) AF: 0.201 AC: 3073 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.0940 AC: 487 AN: 5180

South Asian (SAS) AF: 0.128 AC: 616 AN: 4820

European-Finnish (FIN) AF: 0.234 AC: 2480 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14839 AN: 67976

Other (OTH) AF: 0.204 AC: 430 AN: 2112

Alfa AF: 0.171 Hom.: 399

Bravo AF: 0.159

Asia WGS AF: 0.117 AC: 407 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.65
PhyloP100		0.35
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: rs962001; hg19: chr9-73636237;