Variant chr5-136357175-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020389.3(TRPC7):c.213C>A(p.Phe71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar 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: 0.482

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRPC7	NM_020389.3 linkuse as main transcript	c.213C>A	p.Phe71Leu	missense_variant	2/12	ENST00000513104.6
TRPC7	NM_001376901.1 linkuse as main transcript	c.213C>A	p.Phe71Leu	missense_variant	2/11
TRPC7	NM_001167577.2 linkuse as main transcript	c.213C>A	p.Phe71Leu	missense_variant	2/11
TRPC7	NM_001167576.2 linkuse as main transcript	c.213C>A	p.Phe71Leu	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC7	ENST00000513104.6 linkuse as main transcript	c.213C>A	p.Phe71Leu	missense_variant	2/12	5	NM_020389.3	P1	Q9HCX4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.213C>A (p.F71L) alteration is located in exon 2 (coding exon 2) of the TRPC7 gene. This alteration results from a C to A substitution at nucleotide position 213, causing the phenylalanine (F) at amino acid position 71 to be replaced by a leucine (L). 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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.0042

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.;T;.

Eigen

Benign

-0.012

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.0065

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.6

N;N;.;N

MutationTaster

Benign

0.97

D;D;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.74

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.084

T;D;D;T

Polyphen

0.0010

B;.;B;.

Vest4

0.67

MutPred

0.48

Loss of ubiquitination at K67 (P = 0.1139);Loss of ubiquitination at K67 (P = 0.1139);Loss of ubiquitination at K67 (P = 0.1139);Loss of ubiquitination at K67 (P = 0.1139);

MVP

0.72

MPC

0.93

ClinPred

0.67

GERP RS

5.2

Varity_R

0.22

gMVP

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over