dbSNP rs10521541: TRPC5:c.-22+11543C>T (chrX-112070336-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012471.3(TRPC5):c.-22+11543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 111,068 control chromosomes in the GnomAD database, including 107 homozygotes. There are 922 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 107 hom., 922 hem., cov: 22)

Consequence

TRPC5
NM_012471.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.186

Publications

0 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRPC5	NM_012471.3 link	c.-22+11543C>T	intron_variant	Intron 1 of 10	ENST00000262839.3	NP_036603.1	Q9UL62
TRPC5	XM_017029774.2 link	c.-145+11543C>T	intron_variant	Intron 1 of 11		XP_016885263.1	Q9UL62
TRPC5	XM_047442413.1 link	c.-22+11543C>T	intron_variant	Intron 1 of 9		XP_047298369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC5	ENST00000262839.3 link	c.-22+11543C>T		intron_variant	Intron 1 of 10	1	NM_012471.3	ENSP00000262839.2		Q9UL62

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

3410

AN:

111017

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00190

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00693

Gnomad FIN

AF:

0.00789

Gnomad MID

AF:

0.0508

Gnomad NFE

AF:

0.00724

Gnomad OTH

AF:

0.0227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0307

AC:

3412

AN:

111068

Hom.:

107

Cov.:

AF XY:

0.0277

AC XY:

922

AN XY:

33310

show subpopulations

African (AFR)

AF:

0.0914

AC:

2782

AN:

30442

American (AMR)

AF:

0.0123

AC:

129

AN:

10482

Ashkenazi Jewish (ASJ)

AF:

0.00190

AC:

AN:

2634

East Asian (EAS)

AF:

0.000284

AC:

AN:

3518

South Asian (SAS)

AF:

0.00695

AC:

AN:

2591

European-Finnish (FIN)

AF:

0.00789

AC:

AN:

5960

Middle Eastern (MID)

AF:

0.0558

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00724

AC:

384

AN:

53029

Other (OTH)

AF:

0.0225

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

225

338

450

563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0304

Hom.:

313

Bravo

AF:

0.0339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.30

(source)

DANN

Benign

0.65

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over