rs10521541

Positions:

• chrX-112070336-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC5	NM_012471.3	c.-22+11543C>T		intron_variant		ENST00000262839.3	NP_036603.1
TRPC5	XM_017029774.2	c.-145+11543C>T		intron_variant			XP_016885263.1
TRPC5	XM_047442413.1	c.-22+11543C>T		intron_variant			XP_047298369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC5	ENST00000262839.3	c.-22+11543C>T		intron_variant		1	NM_012471.3	ENSP00000262839.2

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 3410 AN: 111017 Hom.: 107 Cov.: 22 AF XY: 0.0276 AC XY: 917 AN XY: 33249

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.: 22 AF XY: 0.0277 AC XY: 922 AN XY: 33310

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.00190

Gnomad4 EAS AF: 0.000284

Gnomad4 SAS AF: 0.00695

Gnomad4 FIN AF: 0.00789

Gnomad4 NFE AF: 0.00724

Gnomad4 OTH AF: 0.0225

Alfa AF: 0.0290 Hom.: 112

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
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs10521541; hg19: chrX-111313564;