5-136226039-A-T

Variant names:

Variant summary

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

The NM_020389.3(TRPC7):c.2257T>A(p.Phe753Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,438,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000021 ( 0 hom. )

Consequence

TRPC7
NM_020389.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.202

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=0.12881655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3 link	c.2257T>A	p.Phe753Ile	missense_variant	Exon 9 of 12	ENST00000513104.6	NP_065122.1	Q9HCX4-1
TRPC7	NM_001376901.1 link	c.2092T>A	p.Phe698Ile	missense_variant	Exon 8 of 11		NP_001363830.1
TRPC7	NM_001167577.2 link	c.2074T>A	p.Phe692Ile	missense_variant	Exon 8 of 11		NP_001161049.1	Q9HCX4-3
TRPC7	NM_001167576.2 link	c.1909T>A	p.Phe637Ile	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.2257T>A	p.Phe753Ile	missense_variant	Exon 9 of 12	5	NM_020389.3	ENSP00000426070.2		Q9HCX4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1438734

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713246

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33316

American (AMR)

AF:

0.00

AC:

AN:

41330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25664

East Asian (EAS)

AF:

0.00

AC:

AN:

39306

South Asian (SAS)

AF:

0.00

AC:

AN:

82540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1099424

Other (OTH)

AF:

0.00

AC:

AN:

59528

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000009), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2257T>A (p.F753I) alteration is located in exon 9 (coding exon 9) of the TRPC7 gene. This alteration results from a T to A substitution at nucleotide position 2257, causing the phenylalanine (F) at amino acid position 753 to be replaced by an isoleucine (I). 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

0.068

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.18

T;.;T;.

Eigen

Benign

-0.061

Eigen_PC

Benign

0.058

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

N;.;.;.

PhyloP100

0.20

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.15

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.38

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.34

MutPred

0.32

Loss of methylation at K752 (P = 0.0445);.;.;.;

MVP

0.84

MPC

0.87

ClinPred

0.16

GERP RS

3.8

Varity_R

0.070

gMVP

0.28

Mutation Taster

=87/13

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.

5-136226039-A-T

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