rs747346702

Variant names:

• chr20-35004546-C-A
• NM_015638.3:c.1961G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-35004546-C-A
• chr20-35004546-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015638.3(TRPC4AP):​c.1961G>T​(p.Arg654Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRPC4AP NM_015638.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4AP	NM_015638.3	c.1961G>T	p.Arg654Leu	missense_variant	Exon 17 of 19	ENST00000252015.3	NP_056453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC4AP	ENST00000252015.3	c.1961G>T	p.Arg654Leu	missense_variant	Exon 17 of 19	1	NM_015638.3	ENSP00000252015.2
TRPC4AP	ENST00000451813.6	c.1937G>T	p.Arg646Leu	missense_variant	Exon 17 of 19	2		ENSP00000400614.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461600 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727064

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	.;T
Eigen	Benign	0.016
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.13
Sift	Benign	0.033	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.28	.;B
Vest4		0.77
MutPred		0.44		.;Gain of catalytic residue at R654 (P = 0.0622);
MVP		0.082
MPC		0.59
ClinPred		0.75	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33592349;