Genetic Variant NM_020389.3:c.1814G>C (chr5-136247501-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

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:

TRPC7-AS2 (HGNC:40937): (TRPC7 antisense RNA 2)

TRPC7-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020389.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPC7	NM_020389.3	MANE Select	c.1814G>C	p.Arg605Pro	missense	Exon 7 of 12	NP_065122.1	Q9HCX4-1
TRPC7	NM_001376901.1		c.1649G>C	p.Arg550Pro	missense	Exon 6 of 11	NP_001363830.1	Q70T25
TRPC7	NM_001167577.2		c.1631G>C	p.Arg544Pro	missense	Exon 6 of 11	NP_001161049.1	Q9HCX4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPC7	ENST00000513104.6	TSL:5 MANE Select	c.1814G>C	p.Arg605Pro	missense	Exon 7 of 12	ENSP00000426070.2	Q9HCX4-1
TRPC7	ENST00000502753.4	TSL:5	c.1649G>C	p.Arg550Pro	missense	Exon 6 of 11	ENSP00000424854.3	Q70T25
TRPC7	ENST00000378459.7	TSL:5	c.1631G>C	p.Arg544Pro	missense	Exon 6 of 11	ENSP00000367720.3	Q9HCX4-3

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

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111678

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.48

MetaSVM

Pathogenic

0.86

MutationAssessor

Benign

1.2

PhyloP100

5.6

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.9

REVEL

Pathogenic

0.70

Sift

Benign

0.28

Polyphen

0.60

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

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over