20-35038413-C-G

Variant names:

• chr20-35038413-C-G
• rs6087664
• NM_015638.3:c.866-3105G>C

Variant summary

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

The NM_015638.3(TRPC4AP):​c.866-3105G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,750 control chromosomes in the GnomAD database, including 27,158 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 0.59 (27158 hom., cov: 30)
• Consequence: TRPC4AP NM_015638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.71 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4AP	NM_015638.3	MANE Select	c.866-3105G>C		intron	N/A	NP_056453.1
	TRPC4AP	NM_199368.2		c.866-3105G>C		intron	N/A	NP_955400.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4AP	ENST00000252015.3	TSL:1 MANE Select	c.866-3105G>C		intron	N/A	ENSP00000252015.2
	TRPC4AP	ENST00000451813.6	TSL:2	c.866-3105G>C		intron	N/A	ENSP00000400614.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89080 AN: 151632 Hom.: 27132 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.587 AC: 89141 AN: 151750 Hom.: 27158 Cov.: 30 AF XY: 0.591 AC XY: 43841 AN XY: 74126

African (AFR) AF: 0.419 AC: 17290 AN: 41314

American (AMR) AF: 0.721 AC: 10992 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2420 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3577 AN: 5172

South Asian (SAS) AF: 0.582 AC: 2800 AN: 4812

European-Finnish (FIN) AF: 0.668 AC: 7010 AN: 10490

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42785 AN: 67936

Other (OTH) AF: 0.633 AC: 1330 AN: 2100

Alfa AF: 0.473 Hom.: 1324

Bravo AF: 0.591

Asia WGS AF: 0.633 AC: 2197 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.69
PhyloP100		-0.039
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: rs6087664; hg19: chr20-33626216;