9-70775125-G-A

Variant names:

• chr9-70775125-G-A
• rs1831144
• NM_001366145.2:c.1148+8980C>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.1148+8980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,094 control chromosomes in the GnomAD database, including 4,464 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 0.22 (4464 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 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.1148+8980C>T		intron	N/A	NP_001353074.1
	TRPM3	NM_001366147.2		c.1223+8980C>T		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.1154+8980C>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.1148+8980C>T		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.1148+8980C>T		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.1148+8980C>T		intron	N/A	ENSP00000366315.4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33219 AN: 151976 Hom.: 4469 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.233

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: 0.218 AC: 33223 AN: 152094 Hom.: 4464 Cov.: 32 AF XY: 0.217 AC XY: 16094 AN XY: 74310

African (AFR) AF: 0.0643 AC: 2668 AN: 41522

American (AMR) AF: 0.267 AC: 4073 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3468

East Asian (EAS) AF: 0.112 AC: 577 AN: 5166

South Asian (SAS) AF: 0.175 AC: 844 AN: 4820

European-Finnish (FIN) AF: 0.279 AC: 2946 AN: 10556

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20431 AN: 67990

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.240 Hom.: 2110

Bravo AF: 0.214

Asia WGS AF: 0.155 AC: 539 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.044
DANN	Benign	0.49
PhyloP100		-0.85
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: rs1831144; hg19: chr9-73390041;