rs541326

Variant names:

• chr9-71092035-G-A
• rs541326
• NM_001366145.2:c.177+29143C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-71092035-G-A
• chr9-71092035-G-C
• chr9-71092035-G-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.177+29143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,192 control chromosomes in the GnomAD database, including 61,065 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 0.90 (61065 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• 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: 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.177+29143C>T		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.177+29143C>T		intron_variant	Intron 1 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136139 AN: 152074 Hom.: 61027 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.895 AC: 136231 AN: 152192 Hom.: 61065 Cov.: 32 AF XY: 0.899 AC XY: 66874 AN XY: 74386

African (AFR) AF: 0.909 AC: 37769 AN: 41540

American (AMR) AF: 0.922 AC: 14073 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3166 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5158 AN: 5172

South Asian (SAS) AF: 0.921 AC: 4436 AN: 4814

European-Finnish (FIN) AF: 0.907 AC: 9606 AN: 10596

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58986 AN: 68012

Other (OTH) AF: 0.906 AC: 1916 AN: 2114

Alfa AF: 0.885 Hom.: 8977

Bravo AF: 0.896

Asia WGS AF: 0.940 AC: 3269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.78
PhyloP100		0.42
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: rs541326; hg19: chr9-73706951;