4-121902897-CCT-GCG

Variant names:

• chr4-121902897-CCT-GCG
• NM_001130698.2:c.2416_2418delAGGinsCGC
• TRPC3 p.807

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001130698.2(TRPC3):​c.2416_2418delAGGinsCGC​(p.807) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R806R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPC3 NM_001130698.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 publications found

Genes affected

TRPC3 (HGNC:12335): (transient receptor potential cation channel subfamily C member 3) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

TRPC3 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 41

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130698.2. 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
	TRPC3	NM_001130698.2	MANE Select	c.2416_2418delAGGinsCGC	p.807	synonymous	N/A	NP_001124170.1	Q13507-2
	TRPC3	NM_001366479.2		c.2416_2418delAGGinsCGC	p.807	synonymous	N/A	NP_001353408.1
	TRPC3	NM_003305.2		c.2197_2199delAGGinsCGC	p.734	synonymous	N/A	NP_003296.1	Q13507-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC3	ENST00000379645.8	TSL:1 MANE Select	c.2416_2418delAGGinsCGC	p.807	synonymous	N/A	ENSP00000368966.3	Q13507-2
	TRPC3	ENST00000264811.9	TSL:1	c.2197_2199delAGGinsCGC	p.734	synonymous	N/A	ENSP00000264811.5	Q13507-3
	TRPC3	ENST00000513531.1	TSL:1	c.2032_2034delAGGinsCGC	p.679	synonymous	N/A	ENSP00000426899.1	J3QTB0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-122824052;