Variant 12-47667027-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_024604.3(RPAP3):c.1865A>G(p.Lys622Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,385,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RPAP3
NM_024604.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.807

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19995442).

BP6

Variant 12-47667027-T-C is Benign according to our data. Variant chr12-47667027-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2222491.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPAP3	NM_024604.3 linkuse as main transcript	c.1865A>G	p.Lys622Arg	missense_variant	16/17	ENST00000005386.8	NP_078880.2
RPAP3	NM_001146075.2 linkuse as main transcript	c.1763A>G	p.Lys588Arg	missense_variant	15/16		NP_001139547.1
RPAP3	NM_001146076.2 linkuse as main transcript	c.1388A>G	p.Lys463Arg	missense_variant	15/16		NP_001139548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPAP3	ENST00000005386.8 linkuse as main transcript	c.1865A>G	p.Lys622Arg	missense_variant	16/17	2	NM_024604.3	ENSP00000005386	P1	Q9H6T3-1
RPAP3	ENST00000380650.4 linkuse as main transcript	c.1763A>G	p.Lys588Arg	missense_variant	15/16	1		ENSP00000370024		Q9H6T3-2
RPAP3	ENST00000432584.7 linkuse as main transcript	c.1388A>G	p.Lys463Arg	missense_variant	15/16	2		ENSP00000401823		Q9H6T3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1385020

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

688316

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:

0.00000370

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.057

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.016

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.0090

B;.;B

Vest4

0.13

MutPred

0.41

Loss of ubiquitination at K622 (P = 0.0218);.;.;

MVP

0.25

MPC

0.35

ClinPred

0.58

GERP RS

1.9

Varity_R

0.089

gMVP

0.16

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

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