rs3812532

Variant names:

• chr9-70868678-G-T
• rs3812532
• NM_001366145.2:c.178-4167C>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.178-4167C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,758 control chromosomes in the GnomAD database, including 13,570 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 0.42 (13570 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.178-4167C>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.178-4167C>A		intron_variant	Intron 1 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63704 AN: 151642 Hom.: 13555 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.420 AC: 63750 AN: 151758 Hom.: 13570 Cov.: 32 AF XY: 0.418 AC XY: 31020 AN XY: 74188

African (AFR) AF: 0.427 AC: 17667 AN: 41392

American (AMR) AF: 0.461 AC: 7024 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3466

East Asian (EAS) AF: 0.406 AC: 2077 AN: 5120

South Asian (SAS) AF: 0.414 AC: 1991 AN: 4814

European-Finnish (FIN) AF: 0.394 AC: 4164 AN: 10564

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27598 AN: 67872

Other (OTH) AF: 0.434 AC: 917 AN: 2112

Alfa AF: 0.413 Hom.: 3066

Bravo AF: 0.424

Asia WGS AF: 0.412 AC: 1428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.42
DANN	Benign	0.38
PhyloP100		-0.94
PromoterAI		-0.037	Neutral
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: rs3812532; hg19: chr9-73483594;