Variant rs1227678536 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS2_Supporting

The NM_004621.6(TRPC6):c.29G>A(p.Arg10Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000367 in 1,363,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TRPC6
NM_004621.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25315732).

BS2

High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPC6	NM_004621.6 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/13	ENST00000344327.8	NP_004612.2
TRPC6	XM_047427510.1 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/11		XP_047283466.1
TRPC6	XM_017018221.3 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/11		XP_016873710.1
TRPC6	XM_047427509.1 linkuse as main transcript	c.-89+457G>A		intron_variant			XP_047283465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/13	1	NM_004621.6	ENSP00000340913	P1	Q9Y210-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000367

AC:

AN:

1363642

Hom.:

Cov.:

AF XY:

0.00000448

AC XY:

AN XY:

669130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000597

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000282

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.095

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.55

N;.;N;N

MutationTaster

Benign

0.93

N;N;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.41

N;N;N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.016

D;D;D;D

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.21

B;.;B;B

Vest4

0.25

MutPred

0.30

Loss of MoRF binding (P = 0.0105);Loss of MoRF binding (P = 0.0105);Loss of MoRF binding (P = 0.0105);Loss of MoRF binding (P = 0.0105);

MVP

0.78

MPC

0.34

ClinPred

0.34

GERP RS

5.2

Varity_R

0.17

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over