Variant 12-47681778-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024604.3(RPAP3):c.1032A>T(p.Leu344Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,854 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

RPAP3
NM_024604.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.962

Variant links:

Genes affected

RPAP3 (HGNC:26151): (RNA polymerase II associated protein 3) This gene encodes an RNA polymerase II-associated protein. The encoded protein may function in transcriptional regulation and may also regulate apoptosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

RPAP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.097682774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPAP3	NM_024604.3 linkuse as main transcript	c.1032A>T	p.Leu344Phe	missense_variant	10/17	ENST00000005386.8	NP_078880.2
RPAP3	NM_001146075.2 linkuse as main transcript	c.1032A>T	p.Leu344Phe	missense_variant	10/16		NP_001139547.1
RPAP3	NM_001146076.2 linkuse as main transcript	c.555A>T	p.Leu185Phe	missense_variant	9/16		NP_001139548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPAP3	ENST00000005386.8 linkuse as main transcript	c.1032A>T	p.Leu344Phe	missense_variant	10/17	2	NM_024604.3	ENSP00000005386	P1	Q9H6T3-1
RPAP3	ENST00000380650.4 linkuse as main transcript	c.1032A>T	p.Leu344Phe	missense_variant	10/16	1		ENSP00000370024		Q9H6T3-2
RPAP3	ENST00000432584.7 linkuse as main transcript	c.555A>T	p.Leu185Phe	missense_variant	9/16	2		ENSP00000401823		Q9H6T3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725594

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 07, 2023

The c.1032A>T (p.L344F) alteration is located in exon 10 (coding exon 9) of the RPAP3 gene. This alteration results from a A to T substitution at nucleotide position 1032, causing the leucine (L) at amino acid position 344 to be replaced by a phenylalanine (F). 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

Benign

0.067

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.7

DANN

Benign

0.96

DEOGEN2

Benign

0.32

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.098

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.87

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.73

T;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.024

B;.;B

Vest4

0.15

MutPred

0.48

Loss of stability (P = 0.0829);.;Loss of stability (P = 0.0829);

MVP

0.12

MPC

0.16

ClinPred

0.078

GERP RS

-7.3

Varity_R

0.097

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over