dbSNP rs138566611: TRPC5:p.Arg791Trp (chrX-111776864-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_012471.3(TRPC5):c.2371C>T(p.Arg791Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,209,741 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R791R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 8 hem. )

Consequence

TRPC5
NM_012471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Publications

3 publications found

Variant links:

Genes affected

TRPC5 (HGNC:12337): (transient receptor potential cation channel subfamily C member 5) This gene belongs to the transient receptor family. It encodes one of the seven mammalian TRPC (transient receptor potential channel) proteins. The encoded protein is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na(+)-H+ exchange regulatory factor (NHERF ), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1). [provided by RefSeq, May 2010]

TRPC5 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: XL Classification: LIMITED Submitted by: G2P

TRPC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32488412).

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012471.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC5	NM_012471.3	MANE Select	c.2371C>T	p.Arg791Trp	missense	Exon 11 of 11	NP_036603.1	Q9UL62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC5	ENST00000262839.3	TSL:1 MANE Select	c.2371C>T	p.Arg791Trp	missense	Exon 11 of 11	ENSP00000262839.2	Q9UL62

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

111810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000219

AC:

AN:

182426

AF XY:

0.0000447

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1097931

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363321

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26394

American (AMR)

AF:

0.0000284

AC:

AN:

35151

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19369

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54088

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

841989

Other (OTH)

AF:

0.0000434

AC:

AN:

46083

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000268

AC:

AN:

111810

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30770

American (AMR)

AF:

0.00

AC:

AN:

10535

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.00

AC:

AN:

2636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53202

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.55

PhyloP100

2.2

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.17

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Polyphen

0.98

Vest4

0.14

MutPred

0.44

Loss of methylation at R791 (P = 0.0224)

MVP

0.55

MPC

0.36

ClinPred

0.46

GERP RS

4.8

Varity_R

0.38

gMVP

0.57

Mutation Taster

=93/7

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