rs10521536

Positions:

• chrX-111894324-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012471.3(TRPC5):​c.900+17967T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 111,472 control chromosomes in the GnomAD database, including 2,797 homozygotes. There are 5,064 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 0.17 (2797 hom., 5064 hem., cov: 22)
• Consequence: TRPC5 NM_012471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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]

TRPC5OS (HGNC:40593): (TRPC5 opposite strand)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC5	NM_012471.3	c.900+17967T>C		intron_variant		ENST00000262839.3	NP_036603.1
TRPC5OS	NM_001195578.2	c.-545-1627A>G		intron_variant		ENST00000635763.2	NP_001182507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC5	ENST00000262839.3	c.900+17967T>C		intron_variant		1	NM_012471.3	ENSP00000262839.2
TRPC5OS	ENST00000635763.2	c.-545-1627A>G		intron_variant		2	NM_001195578.2	ENSP00000490533.1
TRPC5OS	ENST00000371970.2	c.-545-1627A>G		intron_variant		1		ENSP00000490135.1
TRPC5OS	ENST00000612026.5	c.-545-1627A>G		intron_variant		3		ENSP00000490633.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 18474 AN: 111421 Hom.: 2798 Cov.: 22 AF XY: 0.149 AC XY: 5021 AN XY: 33625

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0320

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.00807

Gnomad MID AF: 0.0730

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.166 AC: 18520 AN: 111472 Hom.: 2797 Cov.: 22 AF XY: 0.150 AC XY: 5064 AN XY: 33686

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.0856

Gnomad4 ASJ AF: 0.0272

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.00807

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0608 Hom.: 3871

Bravo AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs10521536; hg19: chrX-111137552;