NM_015638.3:c.1512-326C>T

Variant names:

• chr20-35009073-G-A
• rs3818253
• NM_015638.3:c.1512-326C>T

Variant summary

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

The NM_015638.3(TRPC4AP):​c.1512-326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,142 control chromosomes in the GnomAD database, including 2,788 homozygotes. 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 0.19 (2788 hom., cov: 32)
• Consequence: TRPC4AP NM_015638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 22 publications found

Genes affected

TRPC4AP (HGNC:16181): (transient receptor potential cation channel subfamily C member 4 associated protein) Enables phosphatase binding activity and ubiquitin ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Part of Cul4A-RING E3 ubiquitin ligase complex. Is active in Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

TRPC4AP Gene-Disease associations (from GenCC):

• hypothyroidism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015638.3. 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
	TRPC4AP	NM_015638.3	MANE Select	c.1512-326C>T		intron	N/A	NP_056453.1	Q8TEL6-1
	TRPC4AP	NM_199368.2		c.1488-326C>T		intron	N/A	NP_955400.1	Q8TEL6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4AP	ENST00000252015.3	TSL:1 MANE Select	c.1512-326C>T		intron	N/A	ENSP00000252015.2	Q8TEL6-1
	TRPC4AP	ENST00000970992.1		c.1512-326C>T		intron	N/A	ENSP00000641051.1
	TRPC4AP	ENST00000888656.1		c.1512-326C>T		intron	N/A	ENSP00000558715.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28697 AN: 152024 Hom.: 2787 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.189 AC: 28701 AN: 152142 Hom.: 2788 Cov.: 32 AF XY: 0.189 AC XY: 14055 AN XY: 74358

African (AFR) AF: 0.187 AC: 7763 AN: 41510

American (AMR) AF: 0.155 AC: 2366 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3470

East Asian (EAS) AF: 0.106 AC: 546 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1245 AN: 4812

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10574

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12901 AN: 67990

Other (OTH) AF: 0.203 AC: 428 AN: 2110

Alfa AF: 0.187 Hom.: 493

Bravo AF: 0.185

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.26
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3818253; hg19: chr20-33596876;