Genetic Variant TRPC7:p.Leu732Phe (chr5-136226102-G-A) – 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_020389.3(TRPC7):c.2194C>T(p.Leu732Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,451,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

TRPC7
NM_020389.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Publications

0 publications found

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:

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=0.2499674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3 link	c.2194C>T	p.Leu732Phe	missense_variant	Exon 9 of 12	ENST00000513104.6	NP_065122.1	Q9HCX4-1
TRPC7	NM_001376901.1 link	c.2029C>T	p.Leu677Phe	missense_variant	Exon 8 of 11		NP_001363830.1
TRPC7	NM_001167577.2 link	c.2011C>T	p.Leu671Phe	missense_variant	Exon 8 of 11		NP_001161049.1	Q9HCX4-3
TRPC7	NM_001167576.2 link	c.1846C>T	p.Leu616Phe	missense_variant	Exon 7 of 10		NP_001161048.1	Q9HCX4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6 link	c.2194C>T	p.Leu732Phe	missense_variant	Exon 9 of 12	5	NM_020389.3	ENSP00000426070.2		Q9HCX4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000173

AC:

AN:

231838

AF XY:

0.0000160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000385

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1451154

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

720572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

43500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25858

East Asian (EAS)

AF:

0.00

AC:

AN:

39566

South Asian (SAS)

AF:

0.00

AC:

AN:

83940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1106384

Other (OTH)

AF:

0.0000167

AC:

AN:

60000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000826

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2194C>T (p.L732F) alteration is located in exon 9 (coding exon 9) of the TRPC7 gene. This alteration results from a C to T substitution at nucleotide position 2194, causing the leucine (L) at amino acid position 732 to be replaced by a phenylalanine (F). 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

Benign

0.11

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.25

T;.;T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.2

L;.;.;.

PhyloP100

3.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.34

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.47

T;T;T;T

Polyphen

0.0010

B;.;B;.

Vest4

0.22

MVP

0.92

MPC

0.68

ClinPred

0.20

GERP RS

5.0

Varity_R

0.14

gMVP

0.43

Mutation Taster

=75/25

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.

chr5-136226102-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over