Variant 20-38057588-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021215.4(RPRD1B):c.472G>C(p.Asp158His) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RPRD1B
NM_021215.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

Variant links:

Genes affected

RPRD1B (HGNC:16209): (regulation of nuclear pre-mRNA domain containing 1B) Enables RNA polymerase II complex binding activity and identical protein binding activity. Involved in positive regulation of cell population proliferation; regulation of cell cycle process; and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of RNA polymerase II, holoenzyme. [provided by Alliance of Genome Resources, Apr 2022]

RPRD1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35345274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPRD1B	NM_021215.4 linkuse as main transcript	c.472G>C	p.Asp158His	missense_variant	4/7	ENST00000373433.9	NP_067038.1
RPRD1B	XM_047440346.1 linkuse as main transcript	c.148G>C	p.Asp50His	missense_variant	2/5		XP_047296302.1
RPRD1B	XM_047440347.1 linkuse as main transcript	c.73G>C	p.Asp25His	missense_variant	2/5		XP_047296303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RPRD1B	ENST00000373433.9 linkuse as main transcript	c.472G>C	p.Asp158His	missense_variant	4/7	1	NM_021215.4	ENSP00000362532	P1
RPRD1B	ENST00000449186.2 linkuse as main transcript	c.118G>C	p.Asp40His	missense_variant	2/5	4		ENSP00000416420
RPRD1B	ENST00000495457.1 linkuse as main transcript	c.338G>C	p.Gly113Ala	missense_variant, NMD_transcript_variant	3/4	4		ENSP00000433947
RPRD1B	ENST00000462548.6 linkuse as main transcript	c.*159G>C		3_prime_UTR_variant, NMD_transcript_variant	3/6	5		ENSP00000436816

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251420

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

EpiCase

AF:

0.0000545

EpiControl

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

Feb 10, 2023

The c.472G>C (p.D158H) alteration is located in exon 4 (coding exon 4) of the RPRD1B gene. This alteration results from a G to C substitution at nucleotide position 472, causing the aspartic acid (D) at amino acid position 158 to be replaced by a histidine (H). 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

0.36

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

T;T

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.13

Sift

Benign

0.12

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.95

P;.

Vest4

0.31

MutPred

0.15

Gain of helix (P = 0.0854);.;

MVP

0.20

MPC

1.4

ClinPred

0.79

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.21

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