Genetic Variant TRPC6:p.Pro15Thr (chr11-101583461-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004621.6(TRPC6):c.43C>A(p.Pro15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,379,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TRPC6
NM_004621.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.11

Publications

0 publications found

Variant links:

Genes affected

TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

TRPC6 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRPC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23187304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004621.6. 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
	TRPC6	NM_004621.6	MANE Select	c.43C>A	p.Pro15Thr	missense	Exon 1 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.43C>A	p.Pro15Thr	missense	Exon 1 of 11	NP_001426264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.43C>A	p.Pro15Thr	missense	Exon 1 of 13	ENSP00000340913.3	Q9Y210-1
TRPC6	ENST00000360497.4	TSL:1	c.43C>A	p.Pro15Thr	missense	Exon 1 of 12	ENSP00000353687.4	Q9Y210-3
TRPC6	ENST00000348423.8	TSL:1	c.43C>A	p.Pro15Thr	missense	Exon 1 of 11	ENSP00000343672.4	Q9Y210-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1379398

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678810

show subpopulations

African (AFR)

AF:

0.0000332

AC:

AN:

30104

American (AMR)

AF:

0.00

AC:

AN:

35360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24652

East Asian (EAS)

AF:

0.00

AC:

AN:

34856

South Asian (SAS)

AF:

0.00

AC:

AN:

78124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1069784

Other (OTH)

AF:

0.00

AC:

AN:

57124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.23

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PhyloP100

3.1

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.60

REVEL

Uncertain

0.34

Sift

Benign

0.086

Sift4G

Benign

0.77

Polyphen

0.048

Vest4

0.21

MutPred

0.29

Gain of phosphorylation at P15 (P = 0.0059)

MVP

0.67

MPC

0.33

ClinPred

0.36

GERP RS

4.6

PromoterAI

0.011

Neutral

(source)

Varity_R

0.092

gMVP

0.44

Mutation Taster

=95/5

polymorphism

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over