rs1998233

Positions:

• chr20-35069323-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015638.3(TRPC4AP):​c.387C>T​(p.Tyr129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,602,508 control chromosomes in the GnomAD database, including 427,776 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 0.77 (45509 hom., cov: 31)
  • Exomes 𝑓: 0.72 (382267 hom.)
• Consequence: TRPC4AP NM_015638.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=2.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC4AP	NM_015638.3	c.387C>T	p.Tyr129=	synonymous_variant	3/19	ENST00000252015.3	NP_056453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC4AP	ENST00000252015.3	c.387C>T	p.Tyr129=	synonymous_variant	3/19	1	NM_015638.3	ENSP00000252015	P4
TRPC4AP	ENST00000451813.6	c.387C>T	p.Tyr129=	synonymous_variant	3/19	2		ENSP00000400614	A1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117104 AN: 151970 Hom.: 45461 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.783

GnomAD3 exomes AF: 0.769 AC: 192832 AN: 250858 Hom.: 74687 AF XY: 0.763 AC XY: 103484 AN XY: 135578

Gnomad AFR exome AF: 0.825

Gnomad AMR exome AF: 0.891

Gnomad ASJ exome AF: 0.793

Gnomad EAS exome AF: 0.761

Gnomad SAS exome AF: 0.720

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.785

GnomAD4 exome AF: 0.724 AC: 1049727 AN: 1450420 Hom.: 382267 Cov.: 31 AF XY: 0.724 AC XY: 523197 AN XY: 722242

Gnomad4 AFR exome AF: 0.826

Gnomad4 AMR exome AF: 0.885

Gnomad4 ASJ exome AF: 0.795

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.722

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.771 AC: 117213 AN: 152088 Hom.: 45509 Cov.: 31 AF XY: 0.774 AC XY: 57559 AN XY: 74336

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.785

Alfa AF: 0.739 Hom.: 96132

Bravo AF: 0.780

Asia WGS AF: 0.768 AC: 2671 AN: 3478

EpiCase AF: 0.739

EpiControl AF: 0.745

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.5
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1998233; hg19: chr20-33657126;