Variant 20-35021259-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_015638.3(TRPC4AP):c.1149T>G(p.His383Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H383L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRPC4AP
NM_015638.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0740

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4AP	NM_015638.3 linkuse as main transcript	c.1149T>G	p.His383Gln	missense_variant	9/19	ENST00000252015.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4AP	ENST00000252015.3 linkuse as main transcript	c.1149T>G	p.His383Gln	missense_variant	9/19	1	NM_015638.3	P4	Q8TEL6-1
TRPC4AP	ENST00000451813.6 linkuse as main transcript	c.1125T>G	p.His375Gln	missense_variant	9/19	2		A1	Q8TEL6-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151366

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000673

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00708

AC:

9573

AN:

1351366

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

4418

AN XY:

675772

show subpopulations

Gnomad4 AFR exome

AF:

0.00606

Gnomad4 AMR exome

AF:

0.000520

Gnomad4 ASJ exome

AF:

0.00288

Gnomad4 EAS exome

AF:

0.00208

Gnomad4 SAS exome

AF:

0.00257

Gnomad4 FIN exome

AF:

0.000615

Gnomad4 NFE exome

AF:

0.00847

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000139

AC:

AN:

151486

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73992

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000580

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000673

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.1149T>G (p.H383Q) alteration is located in exon 9 (coding exon 9) of the TRPC4AP gene. This alteration results from a T to G substitution at nucleotide position 1149, causing the histidine (H) at amino acid position 383 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.62

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.0

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.073

T;T

Sift4G

Uncertain

0.030

D;D

Polyphen

0.99

.;D

Vest4

0.89

MutPred

0.54

.;Loss of ubiquitination at K380 (P = 0.0896);

MVP

0.27

MPC

0.94

ClinPred

0.86

GERP RS

-3.0

Varity_R

0.18

gMVP

0.56

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

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