Variant chr18-36026937-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018170.5(RPRD1A):c.752A>G(p.Gln251Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

RPRD1A
NM_018170.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.97

Variant links:

Genes affected

RPRD1A (HGNC:25560): (regulation of nuclear pre-mRNA domain containing 1A) This gene encodes a cell-cycle and transcription regulatory protein. The encoded protein interacts with the cell cycle inhibitor cyclin-dependent kinase 4 inhibitor B and may function as a negative regulator of G(1)/S phase progression. This protein also forms homo- and hetrodimers with the protein, regulation of nuclear pre-mRNA domain-containing protein 1B, to form a scaffold that interacts with the C-terminal domain of RNA polymerase II subunit B1 and regulates several aspects of transcription. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 16. [provided by RefSeq, Dec 2014]

RPRD1A links:

RPRD1A (HGNC:):

RPRD1A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD1A	NM_018170.5 linkuse as main transcript	c.752A>G	p.Gln251Arg	missense_variant	6/7	ENST00000399022.9	NP_060640.2	Q96P16-1A0A024RC37
RPRD1A	NM_001303413.2 linkuse as main transcript	c.752A>G	p.Gln251Arg	missense_variant	6/7		NP_001290342.1	Q96P16A0A0C4DGQ6
RPRD1A	NM_001303411.2 linkuse as main transcript	c.644A>G	p.Gln215Arg	missense_variant	7/8		NP_001290340.1	Q96P16-3
RPRD1A	NM_001303412.2 linkuse as main transcript	c.644A>G	p.Gln215Arg	missense_variant	7/9		NP_001290341.1	Q96P16-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD1A	ENST00000399022.9 linkuse as main transcript	c.752A>G	p.Gln251Arg	missense_variant	6/7	1	NM_018170.5	ENSP00000381984.3		Q96P16-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.00000756

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

Mar 28, 2024

The c.752A>G (p.Q251R) alteration is located in exon 6 (coding exon 6) of the RPRD1A gene. This alteration results from a A to G substitution at nucleotide position 752, causing the glutamine (Q) at amino acid position 251 to be replaced by an arginine (R). 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

Uncertain

0.54

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;T;T;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;.;D;D

M_CAP

Uncertain

0.097

MetaRNN

Pathogenic

0.89

D;D;D;D

MetaSVM

Uncertain

-0.047

MutationAssessor

Uncertain

2.7

.;M;M;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.4

.;D;D;.

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0040

.;D;D;.

Sift4G

Benign

0.20

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.88

MVP

0.65

MPC

1.1

ClinPred

0.99

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.73

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