chr9-70979198-C-T

Variant names:

• chr9-70979198-C-T
• rs2909295
• NM_001366145.2:c.178-114687G>A

Variant summary

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

The NM_001366145.2(TRPM3):​c.178-114687G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,054 control chromosomes in the GnomAD database, including 34,364 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 0.67 (34364 hom., cov: 31)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.178-114687G>A		intron_variant	Intron 1 of 25	ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.178-114687G>A		intron_variant	Intron 1 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101859 AN: 151934 Hom.: 34337 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.670 AC: 101929 AN: 152054 Hom.: 34364 Cov.: 31 AF XY: 0.671 AC XY: 49847 AN XY: 74314

African (AFR) AF: 0.588 AC: 24360 AN: 41450

American (AMR) AF: 0.667 AC: 10193 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2488 AN: 3466

East Asian (EAS) AF: 0.630 AC: 3254 AN: 5166

South Asian (SAS) AF: 0.729 AC: 3517 AN: 4826

European-Finnish (FIN) AF: 0.678 AC: 7170 AN: 10580

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48614 AN: 67968

Other (OTH) AF: 0.665 AC: 1405 AN: 2114

Alfa AF: 0.696 Hom.: 17936

Bravo AF: 0.662

Asia WGS AF: 0.686 AC: 2389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.78
DANN	Benign	0.74
PhyloP100		-0.61
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: rs2909295; hg19: chr9-73594114; COSMIC: COSV62665310;