rs7050529

Variant names:

• chrX-111912005-G-A
• rs7050529
• NM_012471.3:c.900+286C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-111912005-G-A
• chrX-111912005-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012471.3(TRPC5):​c.900+286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 111,638 control chromosomes in the GnomAD database, including 903 homozygotes. There are 3,541 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 0.11 (903 hom., 3541 hem., cov: 23)
• Consequence: TRPC5 NM_012471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

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.900+286C>T		intron	N/A	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.900+286C>T		intron	N/A	ENSP00000262839.2	Q9UL62

Frequencies

GnomAD3 genomes AF: 0.113 AC: 12611 AN: 111583 Hom.: 907 Cov.: 23

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000565

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0763

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.113 AC: 12631 AN: 111638 Hom.: 903 Cov.: 23 AF XY: 0.105 AC XY: 3541 AN XY: 33856

African (AFR) AF: 0.261 AC: 8009 AN: 30682

American (AMR) AF: 0.0635 AC: 669 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 95 AN: 2639

East Asian (EAS) AF: 0.000567 AC: 2 AN: 3530

South Asian (SAS) AF: 0.0465 AC: 122 AN: 2626

European-Finnish (FIN) AF: 0.0508 AC: 308 AN: 6060

Middle Eastern (MID) AF: 0.0787 AC: 17 AN: 216

European-Non Finnish (NFE) AF: 0.0607 AC: 3224 AN: 53150

Other (OTH) AF: 0.104 AC: 158 AN: 1517

Alfa AF: 0.0739 Hom.: 7133

Bravo AF: 0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	0.71
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7050529; hg19: chrX-111155233;