Variant 20-35006498-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_015638.3(TRPC4AP):c.1764G>A(p.Glu588=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,614,196 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 8 hom. )

Consequence

TRPC4AP
NM_015638.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.652

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 20-35006498-C-T is Benign according to our data. Variant chr20-35006498-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067204.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.652 with no splicing effect.

BS2

High AC in GnomAd4 at 452 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC4AP	NM_015638.3 linkuse as main transcript	c.1764G>A	p.Glu588=	synonymous_variant	15/19	ENST00000252015.3	NP_056453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC4AP	ENST00000252015.3 linkuse as main transcript	c.1764G>A	p.Glu588=	synonymous_variant	15/19	1	NM_015638.3	ENSP00000252015	P4	Q8TEL6-1
TRPC4AP	ENST00000451813.6 linkuse as main transcript	c.1740G>A	p.Glu580=	synonymous_variant	15/19	2		ENSP00000400614	A1	Q8TEL6-3

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

452

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00438

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00283

AC:

711

AN:

251466

Hom.:

AF XY:

0.00288

AC XY:

391

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00444

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00387

AC:

5657

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

2709

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00440

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00455

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00297

AC:

452

AN:

152326

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

223

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00438

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00405

Hom.:

Bravo

AF:

0.00346

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

TRPC4AP: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.9

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over