dbSNP rs191198339: TRPC7:p.Met727Arg (chr5-136226116-A-C) – 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.2180T>G(p.Met727Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,086 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. 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. M727T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRPC7
NM_020389.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

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:

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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=0.23784173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3 link	c.2180T>G	p.Met727Arg	missense_variant	Exon 9 of 12	ENST00000513104.6	NP_065122.1	Q9HCX4-1
TRPC7	NM_001376901.1 link	c.2015T>G	p.Met672Arg	missense_variant	Exon 8 of 11		NP_001363830.1
TRPC7	NM_001167577.2 link	c.1997T>G	p.Met666Arg	missense_variant	Exon 8 of 11		NP_001161049.1	Q9HCX4-3
TRPC7	NM_001167576.2 link	c.1832T>G	p.Met611Arg	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.2180T>G	p.Met727Arg	missense_variant	Exon 9 of 12	5	NM_020389.3	ENSP00000426070.2		Q9HCX4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447086

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

42842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

83484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103980

Other (OTH)

AF:

0.00

AC:

AN:

59844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.17

T;.;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.14

N;.;.;.

PhyloP100

3.4

PrimateAI

Uncertain

0.73

PROVEAN

Benign

1.2

N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.39

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.60

MutPred

0.42

Gain of methylation at K726 (P = 0.0262);.;.;.;

MVP

0.61

MPC

0.95

ClinPred

0.47

GERP RS

5.0

Varity_R

0.50

gMVP

0.54

Mutation Taster

=74/26

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over