Genetic Variant TRPC3:c.2624-17dupT (chr4-121879894-T-TA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001130698.2(TRPC3):c.2624-17dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,517,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TRPC3
NM_001130698.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.707

Publications

0 publications found

Variant links:

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)

TRPC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 4-121879894-T-TA is Benign according to our data. Variant chr4-121879894-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1988034.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 190 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPC3	NM_001130698.2	MANE Select	c.2624-17dupT	intron	N/A	NP_001124170.1	Q13507-2
TRPC3	NM_001366479.2		c.2540-17dupT	intron	N/A	NP_001353408.1
TRPC3	NM_003305.2		c.2405-17dupT	intron	N/A	NP_003296.1	Q13507-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPC3	ENST00000379645.8	TSL:1 MANE Select	c.2624-17_2624-16insT	intron	N/A	ENSP00000368966.3	Q13507-2
TRPC3	ENST00000264811.9	TSL:1	c.2405-17_2405-16insT	intron	N/A	ENSP00000264811.5	Q13507-3
TRPC3	ENST00000513531.1	TSL:1	c.2240-17_2240-16insT	intron	N/A	ENSP00000426899.1	J3QTB0

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

191

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000315

AC:

AN:

171234

AF XY:

0.000283

show subpopulations

Gnomad AFR exome

AF:

0.00428

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

146

AN:

1365568

Hom.:

Cov.:

AF XY:

0.0000918

AC XY:

AN XY:

675060

show subpopulations

African (AFR)

AF:

0.00450

AC:

125

AN:

27772

American (AMR)

AF:

0.000342

AC:

AN:

23378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22950

East Asian (EAS)

AF:

0.00

AC:

AN:

34504

South Asian (SAS)

AF:

0.00

AC:

AN:

70060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51792

Middle Eastern (MID)

AF:

0.000367

AC:

AN:

5456

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073394

Other (OTH)

AF:

0.000196

AC:

AN:

56262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152314

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00435

AC:

181

AN:

41590

American (AMR)

AF:

0.000458

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000783

Hom.:

Bravo

AF:

0.00139

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.71

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over