9-71058243-T-C

Variant names:

• chr9-71058243-T-C
• rs688933
• NM_001366145.2:c.177+62935A>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.177+62935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,138 control chromosomes in the GnomAD database, including 63,047 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 0.91 (63047 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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=-0.91).
• 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+62935A>G		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+62935A>G		intron_variant	Intron 1 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138290 AN: 152020 Hom.: 63001 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.910 AC: 138394 AN: 152138 Hom.: 63047 Cov.: 32 AF XY: 0.912 AC XY: 67836 AN XY: 74386

African (AFR) AF: 0.948 AC: 39373 AN: 41544

American (AMR) AF: 0.929 AC: 14185 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3169 AN: 3466

East Asian (EAS) AF: 0.997 AC: 5144 AN: 5158

South Asian (SAS) AF: 0.925 AC: 4457 AN: 4820

European-Finnish (FIN) AF: 0.909 AC: 9648 AN: 10614

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59357 AN: 67944

Other (OTH) AF: 0.918 AC: 1938 AN: 2110

Alfa AF: 0.891 Hom.: 14665

Bravo AF: 0.913

Asia WGS AF: 0.949 AC: 3300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.50
PhyloP100		-1.4
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: rs688933; hg19: chr9-73673159;