9-71266013-T-G

Variant names:

• chr9-71266013-T-G
• rs10781006
• ENST00000354500.6:n.252+180640A>C

Variant summary

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

The ENST00000354500.6(TRPM3):​n.252+180640A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 152,282 control chromosomes in the GnomAD database, including 72,017 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 0.97 (72017 hom., cov: 32)
• Consequence: TRPM3 ENST00000354500.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354500.6. 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_001366141.2		c.183+180640A>C		intron	N/A	NP_001353070.1
	TRPM3	NM_001366142.2		c.183+180640A>C		intron	N/A	NP_001353071.1
	TRPM3	NM_001366143.2		c.183+180640A>C		intron	N/A	NP_001353072.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000354500.6	TSL:1	n.252+180640A>C		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.183+180640A>C		intron	N/A	ENSP00000350140.2

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147900 AN: 152164 Hom.: 71963 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.978

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

GnomAD4 genome AF: 0.972 AC: 148013 AN: 152282 Hom.: 72017 Cov.: 32 AF XY: 0.973 AC XY: 72453 AN XY: 74440

African (AFR) AF: 0.919 AC: 38175 AN: 41546

American (AMR) AF: 0.983 AC: 15038 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3414 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.995 AC: 4795 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10611 AN: 10616

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67541 AN: 68036

Other (OTH) AF: 0.978 AC: 2067 AN: 2114

Alfa AF: 0.974 Hom.: 10031

Bravo AF: 0.967

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10781006; hg19: chr9-73880929;