NM_012471.3:c.900+17967T>C

Variant names:

• chrX-111894324-A-G
• rs10521536
• NM_012471.3:c.900+17967T>C

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+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
• Publications: 0 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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+17967T>C		intron	N/A	NP_036603.1	Q9UL62
	TRPC5OS	NM_001195578.2	MANE Select	c.-545-1627A>G		intron	N/A	NP_001182507.1	A6NMA1
	TRPC5OS	NM_001195576.1		c.-545-1627A>G		intron	N/A	NP_001182505.1	A6NMA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC5	ENST00000262839.3	TSL:1 MANE Select	c.900+17967T>C		intron	N/A	ENSP00000262839.2	Q9UL62
	TRPC5OS	ENST00000635763.2	TSL:2 MANE Select	c.-545-1627A>G		intron	N/A	ENSP00000490533.1	A6NMA1
	TRPC5OS	ENST00000371970.2	TSL:1	c.-545-1627A>G		intron	N/A	ENSP00000490135.1	A6NMA1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 18474 AN: 111421 Hom.: 2798 Cov.: 22

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

African (AFR) AF: 0.489 AC: 14885 AN: 30412

American (AMR) AF: 0.0856 AC: 899 AN: 10499

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 72 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3589

South Asian (SAS) AF: 0.0214 AC: 57 AN: 2664

European-Finnish (FIN) AF: 0.00807 AC: 49 AN: 6070

Middle Eastern (MID) AF: 0.0798 AC: 17 AN: 213

European-Non Finnish (NFE) AF: 0.0435 AC: 2312 AN: 53168

Other (OTH) AF: 0.136 AC: 207 AN: 1527

Alfa AF: 0.0983 Hom.: 9596

Bravo AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10521536; hg19: chrX-111137552;