NM_001366145.2:c.973+1326T>G

Variant names:

• chr9-70826521-A-C
• rs10117842
• NM_001366145.2:c.973+1326T>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.973+1326T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,096 control chromosomes in the GnomAD database, including 15,286 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 0.44 (15286 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 0 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 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.973+1326T>G		intron	N/A	NP_001353074.1
	TRPM3	NM_001366147.2		c.973+1326T>G		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.979+1326T>G		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.973+1326T>G		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.973+1326T>G		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.973+1326T>G		intron	N/A	ENSP00000366315.4

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66160 AN: 151978 Hom.: 15283 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.443

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.435 AC: 66196 AN: 152096 Hom.: 15286 Cov.: 33 AF XY: 0.434 AC XY: 32286 AN XY: 74356

African (AFR) AF: 0.318 AC: 13211 AN: 41496

American (AMR) AF: 0.433 AC: 6620 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3470

East Asian (EAS) AF: 0.135 AC: 698 AN: 5174

South Asian (SAS) AF: 0.385 AC: 1852 AN: 4812

European-Finnish (FIN) AF: 0.586 AC: 6199 AN: 10584

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34263 AN: 67960

Other (OTH) AF: 0.445 AC: 940 AN: 2114

Alfa AF: 0.477 Hom.: 74610

Bravo AF: 0.419

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		0.079
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: rs10117842; hg19: chr9-73441437;