Genetic Variant TRPC7:p.Asp641Asn (chr5-136231473-C-T) – 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.1921G>A(p.Asp641Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,612,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TRPC7
NM_020389.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22148654).

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.1921G>A	p.Asp641Asn	missense	Exon 8 of 12	NP_065122.1	Q9HCX4-1
TRPC7	NM_001376901.1		c.1756G>A	p.Asp586Asn	missense	Exon 7 of 11	NP_001363830.1	Q70T25
TRPC7	NM_001167577.2		c.1738G>A	p.Asp580Asn	missense	Exon 7 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.1921G>A	p.Asp641Asn	missense	Exon 8 of 12	ENSP00000426070.2	Q9HCX4-1
TRPC7	ENST00000502753.4	TSL:5	c.1756G>A	p.Asp586Asn	missense	Exon 7 of 11	ENSP00000424854.3	Q70T25
TRPC7	ENST00000378459.7	TSL:5	c.1738G>A	p.Asp580Asn	missense	Exon 7 of 11	ENSP00000367720.3	Q9HCX4-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000243

AC:

AN:

246484

AF XY:

0.0000225

show subpopulations

Gnomad AFR exome

AF:

0.0000661

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1460248

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726188

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

85818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111186

Other (OTH)

AF:

0.0000331

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

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

AF:

0.0000394

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000248

AC:

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

Benign

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.013

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

5.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.84

REVEL

Benign

0.28

Sift

Benign

0.72

Polyphen

0.052

Vest4

0.29

MutPred

0.46

Gain of helix (P = 0.062)

MVP

0.88

MPC

0.63

ClinPred

0.40

GERP RS

4.5

Varity_R

0.17

gMVP

0.72

Mutation Taster

=82/18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over