20-35038413-C-G

Position:

• chr20-35038413-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

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 (AMR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC4AP	NM_015638.3	c.866-3105G>C		intron_variant		ENST00000252015.3	NP_056453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC4AP	ENST00000252015.3	c.866-3105G>C		intron_variant		1	NM_015638.3	ENSP00000252015.2
TRPC4AP	ENST00000451813.6	c.866-3105G>C		intron_variant		2		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

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.633

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.69

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: rs6087664; hg19: chr20-33626216;