rs4744628

Variant names:

• chr9-71316862-G-A
• rs4744628
• ENST00000354500.6:n.252+129791C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-71316862-G-A
• chr9-71316862-G-C

Variant summary

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

The NM_001366141.2(TRPM3):​c.183+129791C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,024 control chromosomes in the GnomAD database, including 40,248 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 0.71 (40248 hom., cov: 32)
• Consequence: TRPM3 NM_001366141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• cataract 50 with or without glaucoma

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• 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: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC107987079 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366141.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366141.2		c.183+129791C>T		intron	N/A	NP_001353070.1
	TRPM3	NM_001366142.2		c.183+129791C>T		intron	N/A	NP_001353071.1
	TRPM3	NM_001366143.2		c.183+129791C>T		intron	N/A	NP_001353072.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000354500.6	TSL:1	n.252+129791C>T		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.183+129791C>T		intron	N/A	ENSP00000350140.2	A2A3F7

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107168 AN: 151906 Hom.: 40237 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.705 AC: 107214 AN: 152024 Hom.: 40248 Cov.: 32 AF XY: 0.709 AC XY: 52698 AN XY: 74326

African (AFR) AF: 0.419 AC: 17356 AN: 41390

American (AMR) AF: 0.770 AC: 11759 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2686 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4324 AN: 5176

South Asian (SAS) AF: 0.785 AC: 3780 AN: 4818

European-Finnish (FIN) AF: 0.866 AC: 9169 AN: 10588

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.818 AC: 55618 AN: 67998

Other (OTH) AF: 0.756 AC: 1593 AN: 2108

Alfa AF: 0.787 Hom.: 203616

Bravo AF: 0.687

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.70
PhyloP100		-0.82
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: rs4744628; hg19: chr9-73931778;