Variant 5-136247501-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020389.3(TRPC7):c.1814G>C(p.Arg605Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R605Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRPC7
NM_020389.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

TRPC7 (HGNC:20754): (transient receptor potential cation channel subfamily C member 7) Predicted to enable inositol 1,4,5 trisphosphate binding activity and store-operated calcium channel activity. Predicted to be involved in metal ion transport; regulation of cytosolic calcium ion concentration; and single fertilization. Predicted to act upstream of or within calcium ion transport. Predicted to be located in plasma membrane. Predicted to be part of cation channel complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRPC7 links:

TRPC7-AS2 (HGNC:):

TRPC7-AS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC7	NM_020389.3 linkuse as main transcript	c.1814G>C	p.Arg605Pro	missense_variant	7/12	ENST00000513104.6
TRPC7-AS2	NR_133682.1 linkuse as main transcript	n.59+20788C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC7	ENST00000513104.6 linkuse as main transcript	c.1814G>C	p.Arg605Pro	missense_variant	7/12	5	NM_020389.3	P1	Q9HCX4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00

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

Ambry Genetics

Sep 14, 2023

The c.1814G>C (p.R605P) alteration is located in exon 7 (coding exon 7) of the TRPC7 gene. This alteration results from a G to C substitution at nucleotide position 1814, causing the arginine (R) at amino acid position 605 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;.;D;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Pathogenic

0.86

MutationAssessor

Benign

1.2

L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Pathogenic

0.70

Sift

Benign

0.28

T;T;T;T

Polyphen

0.60

P;.;P;.

Vest4

0.66

MutPred

0.56

Gain of methylation at K608 (P = 0.0576);.;.;.;

MVP

0.93

MPC

1.3

ClinPred

0.96

GERP RS

4.5

Varity_R

0.48

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over